clinical sciences 2 Flashcards
what is the function of leukotrienes?
mediators of inflammation and allergic reactions
causes of bronchoconstriction, mucous production
increases vascular permeability, attracts leukocytes
leukotriene D4 has been identified as the SRS-A (slow reacting substance of anaphylaxis)
where are leukoctienes secreted from?
secreted by leukocytes
what are leukotrienes formed from?
formed from arachidonic acid by action of lipoxygenase
what are examples of mitochondrial disease?
Leber’s optic atrophy
symptoms typically develop at around the age of 30 years
central scotoma → loss of colour vision → rapid onset of significant visual impairment
MELAS syndrome: mitochondrial encephalomyopathy lactic acidosis and stroke-like episodes
MERRF syndrome: myoclonus epilepsy with ragged-red fibres
Kearns-Sayre syndrome: onset in patients < 20 years old, external ophthalmoplegia, retinitis pigmentosa. Ptosis may be seen
sensorineural hearing loss
what would histology of mitochondrial disease show?
muscle biopsy classically shows ‘red, ragged fibres’ due to increased number of mitochondria
how is mitochondria disease inherited?
only via the maternal line
none of the children of an effected male will inherit the disease
all of the children of an affected female will inherit the disease
which immunoglobulin provides immunity to parasites?
IgE
IgE is synthesised to plasma cells
what is suggestive of LBBB?
dominant S wave in V1
QRS > 120ms
what releases interferon gamma?
It is released by natural kill cells and T helper cells (in particular Th1 cells).
what is Achondroplasia?
AD disorder associated with short stature
What is Achondroplasia caused by?
A mutation in the fibroblast growth factor receptor 3 (FGFR-3) gene.
what are the features of achondroplasia ?
short limbs (rhizomelia) with shortened fingers (brachydactyly)
large head with frontal bossing and narrow foramen magnum
midface hypoplasia with a flattened nasal bridge
‘trident’ hands
lumbar lordosis
what is the site of action of ADH?
collecting ducts
what are the boundaries of the popliteal fossa?
Superomedially: Semimembranosus and semitendinosus muscles.
Superolaterally: Biceps femoris muscle.
Inferomedially and Inferolaterally: Medial and lateral heads of the gastrocnemius muscle, respectively.
what are the content of the popliteal fossa?
Popliteal artery
Popliteal vein
Tibial nerve
Common perineal nerve
Popliteal lymph nodes
small saphenous vein
Fat and loose connective tissue
Dermatomes C2 - C8
C2 - posterior half of the skull
C3 - high turtleneck shirt
C4 - low collar shirt
C5 - ventral axial line of upper limb
C6 - thumb and index finger
C7 - middle finger and palm of hand
C8 - ring and little finger
Dermatomes T4 - T10
T4 - nipples
T5 - inframammary fold
T6 - Xiphoid process
T10 - Umbilicus
Dermatomes L1-L5
L1 - inguinal ligament
L4 - knee caps
L5 - big toe, dorm of foot (except lateral aspect)
Dermatomes S1, 2 and 3?
S1 - lateral foot and small toe
S2, S3 - Genitalia
definition of p value?
P value - is the probability of obtaining a result by chance at least as extreme as the one that was actually observed, assuming that the null hypothesis is true
what are microtubules?
Microtubules are components of the cytoskeleton of the cytoplasm. They help guide movement during intracellular transport and also help bind internal organelles. Microtubules are found in all cells except red blood cells.
what is the structure of microtubules?
cylindrical structure composed of alternating α and β tubulin subunits which polymerize to form protofilaments
microtubules are polarized, having a positive and negative end
how do ribosomes help guide intracellular transport?
attachment proteins called dynein and kinesin move up and down the microtubules facilitating the movement of various organelles around the cell
dynein moves in a retrograde fashion, down the microtubule towards the centre of the cell (+ve → -ve)
kinesin moves in an anterograde fashion, up the microtubule away from the centre, towards the periphery (-ve → +ve)
what is falcon syndrome ?
Fanconi syndrome is a disorder of inadequate reabsorption in the proximal convoluted tubules of the kidneys. This commonly presents with hypophosphataemia as well as hyperchloraemia metabolic acidosis, hypokalaemia, and hypocalcaemia.
how do you calculate the likelihood ratio?
Likelihood ratio for a positive test result = sensitivity / (1 - specificity)
Likelihood ratio for a negative test result = (1 - sensitivity) / specificity
what immunological changes are seen in HIV?
reduction in CD4 count
increase B2-microglobulin
decreased IL-2 production
polyclonal B-cell activation
decrease NK cell function
reduced delayed hypersensitivity responses
what is good pasture’s syndrome caused by?
Goodpasture’s syndrome is caused by autoantibodies against collagen type IV
what is the role of collagen Type I
bone skin and tendon
(associated condition - osteogenesis imperfect)
what is the role of collagen Type II ?
Hyaline cartilage, vitreous humour
what is the role of collagen type III?
Reticular fibre, granulation tissue
(Associated conditions -Vascular variant of Ehlers-Danlos syndrome)
What is the role of collagen type IV ?
Basal lamina, lens, basement membrane
Associate conditions - Alport syndrome (mutations in the genes encoding Type IV collagen), Goodpasture’s syndrome (autoimmune reaction where antibodies attack the Type IV collagen)
What is the role of collages type V?
Most interstitial tissue, placental tissue
Associated conditions
Classical variant of Ehlers-Danlos syndrome
what is the structure of collagen?
Collagen is characterised by its triple-helix structure, which consists of three polypeptide chains wound around each other, forming a rope-like assembly that provides tensile strength to tissues.
how is collagen synthesis and secreted?
Synthesis: Collagen synthesis involves several steps, starting with the translation of collagen mRNA to form preprocollagen, which contains extra peptide sequences.
Post-Translational Modifications: Before forming the mature collagen, the procollagen undergoes extensive post-translational modifications such as hydroxylation of proline and lysine residues, crucial for stability and secretion.
Assembly and Secretion: Hydroxylated procollagen forms a triple helix, is processed in the Golgi apparatus, and secreted into the extracellular matrix, where it forms collagen fibres.
what HLA is coeliac disease linked to?
HLA DQ2
what HLA DR3 is Sjogren’s linked to ?
HLA DR3
What key factor is responsible for increase in neutrophils?
IL-8 - main functions include: neutrophil chemotaxis
Function of IL-1
Main source is macrophages
Functions:
acute inflammation
induces fever
Source and function of IL-2
Main source - Th1 cells
Functions: stimulates growth and differenatitaiton of T cell res[onse
Source and function of IL3
Source - activated T helper cells
Functions - stimulates differentiation and proliferation of myeloid progenitor cells
source and function of IL4
Source Th2 cells
function - stimulated proliferation and differentiation of B cells
source and function of IL5
Source Th2 cells
function - stimulates production of eosinophils
source and function of IL6
source - macrophages, Th2 cells
Functions - stimulates differentiation of B cells
Induces fevers
source and function IL8
source - macrophages
Function - neutrophil chemotaxis
source and function IL10
source Th2 cells
function - Inhibits Th1 cytokine production
Also known as human cytokine synthesis inhibitory factor and is an ‘anti-inflammatory’ cytokine
source and function of IL12
Source - Dendritic cells, macrophages, B cells
Functions - Activates NK cells and stimulates differentiation of naive T cells into Th1 cells
Source and function of tumour necrosis factor alpha?
source - macrophages
Functions - induces fever, neutrophil chemotaxis
source and function of interferon-y?
source - Th1 cells
Functions - activates macrophages
what does penetrance and expressivity describe?
Penetrance describes the proportion of a population of individuals who carry a disease-causing allele who express the related disease phenotype. Expressivity describes the extent to which a genotype shows its phenotypic expression in an individual.
Penetrance
describes ‘how likely’ it is that a condition will develop
examples of conditions with incomplete penetrance include retinoblastoma and Huntington’s disease
in contrast, achondroplasia shows 100%, or complete, penetrance
Expressivity
describes the ‘severity’ of the phenotype
a condition with a high level of expressivity is neurofibromatosis
what is p53?
p53 is a tumour suppressor gene located on chromosome 17p. It is the most commonly mutated gene in breast, colon and lung cancer
p53 is thought to play a crucial role in the cell cycle, preventing entry into the S phase until DNA has been checked and repaired. It may also be a key regulator of apoptosis
what is Li-Fraumeni syndrome?
Li-Fraumeni syndrome is a rare autosomal dominant disorder characterised by the early onset of a variety of cancers such as sarcoma, breast cancer and leukaemias. It is caused by mutation in the p53 gene.
Where are HLA antigens encoded?
HLA antigens are encoded for by genes on chromosome 6.
HLA associations?
HLA-A3
haemochromatosis
HLA-B51
Behcet’s disease
HLA-B27
ankylosing spondylitis
reactive arthritis
acute anterior uveitis
psoriatic arthritis
HLA-DQ2/DQ8
coeliac disease
HLA-DR2
narcolepsy
Goodpasture’s
HLA-DR3
dermatitis herpetiformis
Sjogren’s syndrome
primary biliary cirrhosis
HLA-DR4
type 1 diabetes mellitus*
rheumatoid arthritis - in particular the DRB1 gene (DRB104:01 and DRB104:04 hence the association with DR4)
what are the layers of the epidermis?
Stratum corneum - Flat, dead, scale-like cells filled with keratin
Continually shed
Stratum lucidum Clear layer - present in thick skin only
Stratum granulosum Cells form links with neighbours
Stratum spinosum Squamous cells begin keratin synthesis
Thickest layer of epidermis
Stratum germinativum The basement membrane - single layer of columnar epithelial cells
Gives rise to keratinocytes
Contains melanocytes
What is Fabry Disease?
What are the features of Fabry disease?
burning pain/paraesthesia in childhood
angiokeratomas
lens opacities
proteinuria
early cardiovascular disease
What is the function of a peroxisome?
Catabolism of very long chain fatty acids and amino acids
Results in the formation of hydrogen peroxide
What stimulates renin production?
hypotension causing reduced renal perfusion
hyponatraemia
sympathetic nerve stimulation
catecholamines
erect posture
What factors reduce renin secretion?
drugs: beta-blockers, NSAIDs
What is Erythropoiesis?
Erythropoiesis is the process through which red blood cells (erythrocytes) are produced. This occurs in red bone marrow found primarily in flat bones (including the vertebrae, ribs, and sternum) and the proximal ends of long bones in adults. In the foetus, erythrocytes are produced mainly in the liver.
What are all types of blood cells derived from?
All types of blood cells are derived from haematopoietic stem cells. These differentiate into two types of precursor cells: lymphoid and myeloid
What are the stages of development of red blood cell?
What is erythropoiesis regulated by
Erythropoiesis is regulated by erythropoietin (EPO), produced in the kidneys on detection of decreased oxygen levels in the circulation. This increases uptake of iron, heme biosynthesis, and globin gene transcription. Restored oxygen causes a negative feedback loop to the kidney to return to normal production.
Where does the ulnar nerve arise from?
arises from medial cord of brachial plexus (C8, T1)
What is the motor and sensory function on the ulnar nerve?
Motor to
medial two lumbricals
aDductor pollicis
interossei
hypothenar muscles: abductor digiti minimi, flexor digiti minimi
flexor carpi ulnaris
Sensory to
medial 1 1/2 fingers (palmar and dorsal aspects)
Patterns of damage to the ulnar nerve
Damage at wrist
‘claw hand’ - hyperextension of the metacarpophalangeal joints and flexion at the distal and proximal interphalangeal joints of the 4th and 5th digits
wasting and paralysis of intrinsic hand muscles (except lateral two lumbricals)
wasting and paralysis of hypothenar muscles
sensory loss to the medial 1 1/2 fingers (palmar and dorsal aspects)
Damage at elbow
as above (however, ulnar paradox - clawing is more severe in distal lesions)
radial deviation of wrist
What can be used to demonstrate the existance of publication bias?
A funnel plot is primarily used to demonstrate the existence of publication bias in meta-analyses. Funnel plots are usually drawn with treatment effects on the horizontal axis and study size on the vertical axis.
Interpretation
a symmetrical, inverted funnel shape indicates that publication bias is unlikely
conversely, an asymmetrical funnel indicates a relationship between treatment effect and study size. This indicates either publication bias or a systematic difference between smaller and larger studies (‘small study effects’)
What is Edothelin?
Endothelin is a potent, long-acting vasoconstrictor and bronchoconstrictor. It is secreted initially as a prohormone by the vascular endothelium and later converted to ET-1 by the action of endothelin converting enzyme. It acts via interaction with a G-protein linked to phospholipase C leading to calcium release. Endothelin is thought to be important in the pathogenesis of many diseases including primary pulmonary hypertension (endothelin antagonists are now used), cardiac failure, hepatorenal syndrome and Raynaud’s.
What promotes and inhibits endothelin release ?
Promotes release
angiotensin II
ADH
hypoxia
mechanical shearing forces
Inhibits release
nitric oxide
prostacyclin
In what conditions do you see a raised Endothelin level?
primary pulmonary hypertension
myocardial infarction
heart failure
acute kidney injury
asthma
Why do reticulocytes look like when they are stained?
Reticulocytes have a mesh-like (reticular) network of ribosomal RNA that is visible when stained. This is not present in mature erythrocytes
What is the mechanism of action of Anakinra?
Anakinra is an interleukin-1 (IL-1) receptor antagonist. Interleukin-1 refers to a ‘superfamily’ of 11 cytokines that are responsible for acute inflammation and inducing fever. Blocking IL-1 with anakinra is beneficial in pro-inflammatory conditions such as rheumatoid arthritis. Il-1 is predominantly secreted by macrophages.
Which cytokine is involved in neutrophil chemotaxis?
IL8
Where does the majority of glucose reabsorption in the nephron occur in the kidney ?
The majority of glucose reabsorption in the nephron occurs within the proximal convoluted tubule
what does vitamin D do to calcium and phosphate levels?
Vitamin D increases plasma calcium and plasma phosphate levels by promoting renal tubular absorption and gut absorption of calcium and increasing renal phosphate reabsorption
What two hormones primarily control calcium metabolism?
parathyroid hormone (PTH)
1,25-dihydroxycholecalciferol (calcitriol, the active form of vitamin D)
Actions of PTH?
increases plasma calcium, decreases plasma phosphate
increases renal tubular reabsorption of calcium
increases osteoclastic activity*
increases renal conversion of 25-hydroxycholecalciferol to 1,25-dihydroxycholecalciferol
decreases renal phosphate reabsorption
Actions of vitamin D?
increases plasma calcium and plasma phosphate
increases renal tubular reabsorption and gut absorption (small intestine) of calcium
increases osteoclastic activity
increases renal phosphate reabsorption
What is responsible for the rapid depolarisation phase of the myocardial action potential?
Rapid sodium influx
what is the usual outcome measures in a case control study?
The usual outcome measure is the odds ratio.
Musculoctaneous nerve
what is the motor and sensory function?
What are the typical mechanisms of injury?
C5-C7
Motor- elbow flexion (supplies biceps brachii) and supination
Sensory - lateral aspect of the forearm
Isolated injury rare - usually injured as part of brachial plexus injury
Axillary nerve
what is the motor and sensory function?
What are the typical mechanisms of injury?
C5-C6
Motor - shoulder abduction (deltoid muscle)
Sensory - inferior region of the deltoid muscle
Humeral neck fracture/dislocation
Results in flattened deltoid
Radial nerve
what is the motor and sensory function?
What are the typical mechanisms of injury?
C5-C8
Motor - extension (forearm, wrist, thumb, fingers)
Sensory - small area between the dorsal aspect of the 1st and2nd metacarpals
Humeral midshaft fracture
Palsy results in wrist drop
Median nerve
what is the motor and sensory function?
What are the typical mechanisms of injury?
C6, C8, T1
Motor - LOAF muscles
Features depend on the site of the lesion:
wrist: paralysis of thenar muscles, opponens pollicis
elbow: loss of pronation of forearm and weak wrist flexion
Sensory - palmer aspect of lateral 3 1/2 fingers
Wrist lesion –> ccarpal tunnel syndrome
Ulnar nerve
what is the motor and sensory function?
What are the typical mechanisms of injury?
C8-T1
Motor - Intrinsic hand muscles except LOAF*
Sensory - Wrist flexion Medial 1½ fingers Medial epicondyle fracture
Damage may result in a ‘claw hand’
Long thoracic nerve?
Motor function
Typical mechanism injury
Motor function - serratus anterior
Often during sport e.g. following a blow to the ribs. Also possible complication of mastectomy
Damage results in a winged scapula
What are the LOAF muscles?
Lateral two lumbricals
Opponens pollis
Abductor pollis brevis
Flexor pollis brevis
what is Erb-Duchenne palsy ?
Erb-Duchenne palsy (‘waiter’s tip’)
due to damage of the upper trunk of the brachial plexus (C5,C6)
may be secondary to shoulder dystocia during birth
the arm hangs by the side and is internally rotated, elbow extended
What is Klumpke injury?
due to damage of the lower trunk of the brachial plexus (C8, T1)
as above, may be secondary to shoulder dystocia during birth. Also may be caused by a sudden upward jerk of the hand
associated with Horner’s syndrome
What is IgE synthesised by?
Plasma cells
Which immungloblin mediates type 1 hypersenstivity reactions ?
IgE
IgE
What conditions are inherited in an X-linked dominant fashion?
Alport’s syndrome (in around 85% of cases - 10-15% of cases are inherited in an autosomal recessive fashion with rare autosomal dominant variants existing)
Rett syndrome
Vitamin D resistant rickets
*pseudohypoparathyroidism was previously classified as an X-linked dominant condition but has now been shown to be inherited in an autosomal dominant fashion in the majority of cases
what is penetrance and expressivity?
Penetrance
describes ‘how likely’ it is that a condition will develop
examples of conditions with incomplete penetrance include retinoblastoma and Huntington’s disease
in contrast, achondroplasia shows 100%, or complete, penetrance
Expressivity
describes the ‘severity’ of the phenotype
a condition with a high level of expressivity is neurofibromatosis
During cell division, at what stage do sister chromatids move to opposite ends of the cell?
During mitosis, sister chromatids move to opposite ends of the cell during anaphase
Pathophysiology of artherosclerosis?
initial endothelial dysfunction is triggered by a number of factors such as smoking, hypertension and hyperglycaemia
this results in a number of changes to the endothelium including pro-inflammatory, pro-oxidant, proliferative and reduced nitric oxide bioavailability
fatty infiltration of the subendothelial space by low-density lipoprotein (LDL) particles
monocytes migrate from the blood and differentiate into macrophages. These macrophages then phagocytose oxidized LDL, slowly turning into large ‘foam cells’. As these macrophages die the result can further propagate the inflammatory process.
smooth muscle proliferation and migration from the tunica media into the intima results in formation of a fibrous capsule covering the fatty plaque.
what technique can be used to look for the HER2 gene?
fluorescence in situ hybridisation (FISH). This is a technique using fluorescent DNA (or RNA) probes that bind to specific genomic sites of interest, to directly visualise chromosomal abnormalities - e.g. HER2 gener
