Clinical sciences Flashcards
what is the normal daily fluid requirements?
25-30ml/kg daily
What is ANP?
Atrial Natiuretic peptide
It is released by the atria of the heart
It is secreted in response to an increase in blood volume
It targets the kidneys and causes a decrease in sodium reabsorption and so more sodium exits the body
Water follows the sodium and so fluid volume decreases.
This will decrease blood volume and pressure
ANP promotes vasodilations of blood vessels
ANP increases GFR by vasodilating the afferent arteriole in the nephron. This increases the amount of water and sodium excreted by the kidneys
It inhibits the the renin angiotensin system, reduces aldosteronee secretion by the adrenal glands and releases free fatty acids from adipose tissue
what percentage of the body fluids is intracellular vs extracellular?
two thirds is intracellular
one third is extracellular
how is maintenance fluids calculated?
100mls/kg/day for the first 10kg of body weight
50mls/kg/day for the next 10kg of body weight
20mls/kg/day for every kg > 20 kg
what is the pathophysiology of transplant rejection?
the immune system must be able to distinguish between self and non-self
foreign invaders such as bacteria and viruses are presented to the immune system as non-self antigens which trigger an immune response via antibodies which mark the infected cells for destruction
Human Leukocyte antigen complexes are a group of proteins that are found on the surface of all cells in the body.
They help the immune system to distinguish the body’s own proteins from those that are produced by foreign viruses an/or bacteria, thereby ensuring that cells of the persons own body are not triggered for destruction accidentally
Each individual will have a specific group of HLA proteins which present on their own cells - their immune system will have learned not to react to this - there for any cells not displaying these proteins will be indentified as foreign
Graft rejection occurs when the recipient’s immune system regard the transplant as foreign.
The immune response is triggered by the presence of the donor’s unique HLA proteins on the transplanted tissues which is identified as foreign.
There will always be a degree of rejection unless the donor and recipient are identical twins
what are the stages of transplant rejection
hyper acute - minutes to hours - caused by pre-existing antibodies of the recipient that match the foreign antigens of the donor, triggering a response . Antibodies react with cells in the graft blood vessels causing clots to form and the oxygen supply to the great will be compromised
Acute - 6 months - causes by antibody formation when non-self antigens from the donor graft are recognised by the recipients immune system - this risk is highest in the first three months
Chronic - months to years - repeated episodes of acute rejection can lead to chronic rejection which manifests as scarring of the tissue or oran. The graft will have to be removed.
which HLA is involved in hyper acute rejection?
HLA-C
How do arteriosclerosis form?
The earliest lesions of atherosclerosis are fatty streaks. These consist of an accumulation of lipid-egorged macrophages (foam cells). The fatty streaks progress to intermediate lesions (or transitional plaque), which are composed mainly of macrophage foam cells and small muscle cells which migrate into the intimate from the media. With time, these develop into raised fibrous (advanced) plaques, characterised by a dense fibrous cap of connective tissue and smooth muscle cells overlying a core containing necrotic material and lipid, mainly cholesterol esters which may form cholesterol crystal on histological section.
What is the pathology if a patients has horizontal diplopia, worsens when looking to one side and improves on covering up that eye?
Abducens nerve palsy
The abducens nerve, AKA the 6th cranial nerve, innervates the lateral rectus muscle in the eye. This muscle is responsible for abduction or outward gaze
When there is a lesion or damage to this nerve, it results in an inability to abduct the affected eye leading to horizontal diplopia (double vision). This double vision worsens when looking towards the side of the affected eye (in this case, right) due to unopposed action of medial rectus muscle and improves upon covering that eye.
what may abdomen nerve palsy be caused by?
by several factors including diabetic neuropathy, as seen in this patient with a history of type 1 diabetes mellitus. Other causes include increased intracranial pressure, trauma or infections like Lyme disease. Management would typically involve addressing any underlying cause if identified and symptomatic relief through prismatic glasses or eventually strabismus surgery if required.
What is Cranial nerve one?
Olfactory nerve
Functions - smell
Foramen - cribriform plate
What is cranial nerve two ?
Optic neve
Function - sight
Foramen - optical canal
What is cranial never three?
Oculomotor nerve
Functions - eye movement - MR, IO, SR, IR), pupil constriction, accommodation, Eyelid opening
Palsy results in - ptosis, ‘down and out’ eye, dilated fix pupil
Foramen - superior orbital fissure
What is cranial nerve four?
Trochlear nerve
Functions: eye movement (SO)
Palsy results in defective downward glaze –> vertical diplopia
Foramen SOF
What is cranial nerve five?
Trigeminal
Functions : facial sensation and mastication
Lesions may cause
- trigeminal neuralgia
- lossof corneal reflex (afferent)
- Loss of facial sensation
- paralysis of the mastication muscles
- deviation of the jaw to the weak side
Foramen
V1: SOF, V2: Foramen rotundum,
V3: Foramen ovale
What is cranial nerve six?
VI - abducens
functions - eye movement (LR)
Palsy results in defective abduction –> horizontal diplopia
Foramen - SOF
What is cranial nerve seven?
VII facial
Functions: Facial movement, taste (anterior 2/3rds of tongue) lacrimation, salivation
Lesions may results in:
- flaccid paralysis of the upper and lower face
- loss of corneal reflex (efferent)
- loss of taste
- hyperacusis
Foramen - internal auditory meatus
What is cranial nerve eight?
VIII - Vestibulocochlear
Function - hearing and balance
Hearing loss
Vertigo, nystagmus
Acoustic neuromas are Schwann cell tumours of the cochlear nerve
foramen - internal auditory meatus
What is cranial nerve nine?
IX - glossopharyngeal
Function - Taste (posterior 1/3rd of tongue), Salivation, Swallowing, Mediates input from carotid body & sinus
Lesions may result in; hypersensitive carotid sinus reflex loss of gag reflex (afferent)
Foramen - jugular foramen
What is cranial nerve ten?
X - Vagus nerve
Function - phonation, swallowing, innervates viscera
Lesions may result in - uvula deviates away from the site of the lesion, loss of gag reflex efferent
Foramen - jugular foramen
What is cranial nerve eleven?
XI - accessory
Function - head and shoulder movement
Lesions - may result in weakness turning head to contralateral side
Foramen - jugular foramen
What is cranial nerve twelve?
XII - hypoglossal
Function - tongue movement
Lesions may result in tongue deviation towards the side of the lesion
Foramen - hypoglossal canal
Which cranial nerves are sensory vs motor?
Some Say Marry Money But My Brother Says Big Brains Matter Most
S = Sensory, M = Motor, B = Both
What is the afferent and efferent limbs of the corneal reflex?
Afferent - Ophthalmic
Efferent - Facial
What is the afferent and efferent limbs of the jaw jerk?
Afferent - Mandibular V3
Efferent - mandibular V3
What is the afferent and efferent limbs of the gag reflex?
Afferent - glossopharyngeal nerve
efferent - vagal nerve
What is the afferent and efferent limbs of the carotid sinus ?
Afferent - glossopharyngeal nerve
Efferent - vagal nerve
What is the afferent and efferent limbs of the pupillary light reflex?
Afferent - optic nerve
Efferent - occulmototor nerve
What is the risk of Down’s with material age?
Age (years) Risk
20 1 in 1,500
30 1 in 800
35 1 in 270
40 1 in 100
45 1 in 50 or greater
What cancers are EBV associated with?
Burkitt’s lymphoma
Hodgkin’s lymphoma
Post transplant lymphoma
Nasopharyngeal carcinoma
What cancers are HPV 16/18 associated with?
Cervical cancer
Anal cancer
Penile cancer
Vulval cancer
Oropharyngeal cancer
What cancer is human herpes virus 8 associated with?
Kaposi’s sarcoma
What cancer is Hep B associated with ?
hepatocellular carcinoma
What cancer is hep C associated with ?
Hepatocellular carcinoma
what cancer is human T-lymphotrophic virus associated with ?
Tropical spastic paraparesis
Adult T cell leukaemia
what is a common renal abnormality in turners syndrome?
Horseshoe Kidney
What is turners syndrome?
Turner’s syndrome is a chromosomal disorder affecting around 1 in 2,500 females. It is caused by either the presence of only one sex chromosome (X) or a deletion of the short arm of one of the X chromosomes. Turner’s syndrome is denoted as 45,XO or 45,X.
what are the features of turners syndrome?
short stature
shield chest, widely spaced nipples
webbed neck
bicuspid aortic valve (15%), coarctation of the aorta (5-10%)
an increased risk of aortic dilatation and dissection are the most serious long-term health problems for women with Turner’s syndrome
regular monitoring in adult life for these complications is an important component of care
primary amenorrhoea
cystic hygroma (often diagnosed prenatally)
high-arched palate
short fourth metacarpal
multiple pigmented naevi
lymphoedema in neonates (especially feet)
gonadotrophin levels will be elevated
hypothyroidism is much more common in Turner’s
horseshoe kidney: the most common renal abnormality in Turner’s syndrome
What are the subsets of T-helper cells?
Th1
involved in the cell-mediated response and delayed (type IV) hypersensitivity
secrete IFN-gamma, IL-2, IL-3
Th2
involved in mediating humoral (antibody) immunity
e.g. stimulating production of IgE in asthma
secrete IL-4, IL-5, IL-6, IL-10, IL-13
What are the features of congenital rubella?
Sensorineural deafness
Congenital cataracts
Congenital heart disease (e.g. patent ductus arteriosus)
Glaucoma
Growth retardation
Hepatosplenomegaly
Purpuric skin lesions
‘Salt and pepper’ chorioretinitis
Microphthalmia
Cerebral palsy
what are the features of congenital toxoplasmosis?
Cerebral calcification
Chorioretinitis
Hydrocephalus
anaemia
hepatosplenomegaly
cerebral palsy
what are the features of congenital CMV?
Low birth weight
Purpuric skin lesions
Sensorineural deafness
Microcephaly
Visual impairment
Learning disability
Encephalitis/seizures
Pneumonitis
Hepatosplenomegaly
Anaemia
Jaundice
Cerebral palsy
what is the respiratory physiology associated with hypoxia?
A fall in the partial pressure of oxygen in the blood leads to vasoconstriction of the pulmonary arteries. This allows blood to be diverted to better aerated areas of the lung and improves the efficiency of gaseous exchange
what are the two types of cell devision?
Mitosis - occurs in somatic cells, results in 2 diploid daughter cells, daughter cells are genetically identical to parent cell
Meiosis - occurs in gametes, results in 4 haploid daughter cells, daughter cells contain one homologue of each chromosome pain and therefore are genetically different
what are the phases of mitosis?
Prometaphase Nuclear membrane breaks down allowing the microtubules to attach to the chromosomes
Metaphase Chromosomes aligned at middle of cell
Anaphase The paired chromosomes separate at the kinetochores and move to opposite sides of the cell
Telophase Chromatids arrive at opposite poles of cell
Cytokinesis Actin-myosin complex in the centre of the cell contacts resulting in it being ‘pinched’ into two daughter cells
What is interphase?
Interphase is the phase in the cell cycle characterised by the increased cell size and DNA replication in preparation for cell devision.
G1 - cell growth
S phase - replication of the chromosomes (DNA synthesis)
G2 - growth and preparation for mitosis
M - mitosis
what complement deficiency predisposes to Neisseria meningitides?
C5-9 deficiency
The complement proteins C5, C6, C7, C8 and C9 together form the membrane attack complex which acts to cause cell lysis and death of pathogens. A deficiency in these proteins increases the susceptibility to infections, particularly Neisseria meningitidis infections.
what does a C1 inhibitor protein deficiency cause?
A C1 inhibitor protein deficiency is the cause of hereditary angioedema. The disease presents as spontaneous angioedema likely secondary to uncontrolled release of bradykinin resulting in oedema of the soft tissues of the face.
what does deficiency in complement protein C3 lead to?
Current recurrent bacterial infections
The complement protein C3 is needed for opsonisation and a deficiency in this protein predisposes patients to overwhelming infections with encapsulated organisms. The significance of recurrent infections in C3 deficiency is more severe than that of C5-9 deficiency and tends to present at an earlier age with an increased risk of mortality.
What does C1q, C1rs, C2, C4 deficiency lead to?
predisposes to immune complex disease
e.g. SLE, Henoch-Schonlein Purpura
What does C5 deficiency lead to?
predisposes to Leiner disease
recurrent diarrhoea, wasting and seborrhoeic dermatitis
What is the complement system?
The complement system, an integral part of the innate immune system, consists of a series of plasma proteins that collaborate to eradicate pathogens, promote inflammation, and fine-tune the adaptive immune response. Complement proteins are involved in chemotaxis, cell lysis and opsonisation. Deficiencies in the complement system can increase susceptibility to infections, autoimmune disorders, or other conditions.
What are the sleep stages?
Non-REM stage 1 (N1)
EEG : Theta waves
Light sleep
Transition to this stage be associated with hypnic jerks
Non-REM stage 2 (N2)
EEG: Sleep spindles + K-complexes
Deeper sleep
Represents around 50% of total sleep
Non-REM stage 3 (N3)
EEG: Delta waves
Deep sleep
Parasomnias such as night terrors, nocturnal enuresis, sleepwalking
REM
EEG: Beta-waves
Dreaming occurs
Loss of muscle tone, erections
Where is phosphate reabsorbed in the kidney?
the proximal tubule
what hormones are involved with calcium metabolism?
Parathyroid hormone (PTH)
Increase calcium levels and decrease phosphate levels
Increases bone resorption
Immediate action on osteoblasts to increase ca2+ in extracellular fluid
Osteoblasts produce a protein signaling molecule that activate osteoclasts which cause bone resorption
Increases renal tubular reabsorption of calcium
Increases synthesis of 1,25(OH)2D (active form of vitamin D) in the kidney which increases bowel absorption of Ca2+
Decreases renal phosphate reabsorption
1,25-dihydroxycholecalciferol (the active form of vitamin D)
Increases plasma calcium and plasma phosphate
Increases renal tubular reabsorption and gut absorption of calcium
Increases osteoclastic activity
Increases renal phosphate reabsorption in the proximal tubule
Calcitonin
Secreted by C cells of thyroid
Inhibits osteoclast activity
Inhibits renal tubular absorption of calcium
what is lung compliance?
lung compliance is defined as a change in lung volume per unit change in air way pressure
what causes increased lung compliance?
age
emphysema - this is due to loss alveolar walls and associated elastic tissue
what causes decreased lung compliance?
pulmonary oedema
pulmonary fibrosis
pneumonectomy
kyphosis
what is PCR?
Polymerase chain reaction (PCR) is a molecular genetic investigation technique. The main advantage of PCR is its sensitivity: only one strand of sample DNA is needed to detect a particular DNA sequence. It now has many uses including prenatal diagnosis, detection of mutated oncogenes and diagnosis of infections. PCR is also extensively used in forensics. Prior to the procedure, it is necessary to have two DNA oligonucleotide primers. These are complementary to specific DNA sequences at either end of the target DNA
How is PCR carried out?
Initial prep
sample of DNA is added to the test tube along with two DNA primers
a thermostable DNA polymerase (Taq) is added
The following cycle then takes place
mixture is heated to almost boiling point causing denaturing (uncoiling) of DNA
mixture is then allowed to cool: complimentary strands of DNA pair up, as there is an excess of the primer sequences they pair with DNA preferentially
The above cycle is then repeated, with the amount of DNA doubling each time
Reverse transcriptase PCR
used to amplify RNA
RNA is converted to DNA by reverse transcriptase
gene expression in the form of mRNA (rather than the actually DNA sequence) can therefore be analyzed
What is Batter’s syndrome?
Bartter syndrome is a rare inherited disease characterised by a defect in the thick ascending limb of the loop of Henle, which results in low potassium levels, increased blood pH, and normal to low blood pressure.
Polyhydramnios is typical in the neonatal form of Bartter’s syndrome.
What are some causes of metabolic alkalosis?
vomiting / aspiration
(e.g. peptic ulcer leading to pyloric stenos, nasogastric suction)
vomiting may also lead to hypokalaemia
diuretics
liquorice, carbenoxolone
hypokalaemia
primary hyperaldosteronism
Cushing’s syndrome
Bartter’s syndrome
how is the standard error of the mean calculated?
Standard error of the mean = standard deviation / square root (number of patients)
what is fabry disease ?
X-linked recessive
deficiency of alpha-galactosidase A
Fabry disease is a disorder of lysosomal storage and deficiency of alpha-galactosidase A
what are the features of fabry disease?
burning pain/paraesthesia in childhood
angiokeratomas
lens opacities
proteinuria
early cardiovascular disease
What does C5-9 deficiency?
encodes the membrane attack complex (MAC)
particularly prone to Neisseria meningitidis infection
what is the hiring-bruer reflex?
Lung distension causing slowing of the respiratory rate
It is a physiological reflex that prevents over inflation of the lungs. It involves stretch receptors in the lung paranchyma which send inhibitory signals to the medullary respiratory centre via the vagus nerve when the lungs become overly distended during inspiration. this ultimately results in decrease in the respiratory rate and volume protecting against potential lung damage from over-inflation.
what area of the brain control respiration?
medulla oblongata
What are the anatomical components of the medullary respiratory centre?
Dorsal respiratory group
Ventral respiratory group
where is the respiratory rhythm generator?
The ventral respiratory group is the other main complex of neurones in the medullary respiratory centre. The respiratory rhythm generator is located in the pre-Botzinger complex of neurones in the upper part of the VRG. The rhythm generator appears to be composed of pacemaker cells and a complex neuronal network that acting together set the basal respiratory rate.
where are expiratory neurones?
the ventral respirator group contains expiratory neurones that appear to be important when large increases in ventilation are required.
where are pulmonary stretch receptors?
they lie in the airway smooth muscle layer are activated by a large lung inflation - these lead to inhibition of the activity of the medullary inspiratory neurones. (Hearing-Breuer reflex)
this reflex only really plays. role in setting respiratory rhythm under conditions od very large tidal volumes - e.g. in strenuous exercise
what may inhibit medullary inspiratory neurones?
drugs such as barbiturates and opioids.
where does the most important input for the medullary inspiratory neurones come from at res?
peripheral (arterial) chemoreceptors and central chemoreceptors
where are the peripheral chemoreceptors located?
carotid arteries and the arch of the aorta
aka
carotid bodies and aortic bodies
what are the peripheral chemoreceptors stimulated by?
decrease in arterial Po2 and increase in arterial hydrogen concentration
this leads to excitatory synaptic input to the medullary inspiratory neurones
where are central chemoreceptors located?
medulla
like peripheral chemoreceptors they provide excitatory synaptic input to the medullary inspiratory neurones
what are the central chemoreceptors stimulated by?
an increase in hydrogen concentration of the brains extracellular fluid
what factors lead to a role in stimulating ventilation during exercise ?
mechanoreceptors in the joints and muscles
increase in body temp
motor cortex
increase in the plasma epinephrine concentration
increase in plasma potassium
conditioned response
what is Di-George syndrome?
a primary immunodeficiency disorder caused by T-cell deficiency and dysfunction
a micro deletion syndrome - deletion of a section of chromosome 22
aka velocardiofacial syndrome and 22q11.2 deletion syndrome
how is Di-George syndrome inherited?
AD
what are the features of DiGeorge syndrome?
at risk of viral and fungal infections
parathyroid gland hypoplasia → hypocalcaemic tetany
thymus hypoplasia
T-lymphocyte deficiency/dysfunction
It has a variable presentation however its features can be remembered with the mnemonic CATCH22:
C - Cardiac abnormalities
A - Abnormal facies
T - Thymic aplasia
C - Cleft palate
H - Hypocalcaemia/ hypoparathyroidism
22 - Caused by chromosome 22 deletion
what are cytokines?
general term for protein messenger that regulate immune responses - secreted by macrophages, monocytes, lymphocytes, neutrophils and several non immune cell types
they function both locally and as hormones.
what are interferons?
Interferons are cytokines released by the body in response to viral infection and neoplasia.
what are the different types of interferon?
IFN-alpha and IFN-beta bind to type 1 receptors whilst IFN-gamma binds only to type 2 receptors.
what is the source interferon gamma?
natural killer cells and activated T helper cells
what is the function of interferon gamma?
stimulate proliferation and secretion on cytotoxic compounds
what is the mechanism of action of anti-diuretic hormone?
it promotes water reabsorption by the insertion of aquaporin-2-channels
what is the source of ADH?
synthesised in the supraoptic nuclei of the hypothalamus, released by the posterior pituitary
how is ADH regulated?
it is secreted in response to
- extracellular fluid osmolality increase
- volume decrease
- pressure decrease
- angiotensin II
secretion decreased in response to
- extracellular fluid osmolality decrease
- volume increase
- temp decrease
how is LV ejection fraction calculated?
stroke volume / end diastolic volume
how is cardiac output calculated
stroke volume x heart rate
how is stroke volume calculated ?
end diastolic LV volume - end systolic LV volume
what is pulse pressure ?
systolic pressure - diastolic pressure
what factors increase pulse pressure
a less compliant aorta (this tends to occur with advancing age)
increased stroke volume
how is systemic vascular resistance calculated?
Systemic vascular resistance = mean arterial pressure / cardiac output
what is the main function of the endoplasmic reticulum?
Rough endoplasmic reticulum - translation and folding of new proteins, manufacture of lysosomal enzymes, site of N- linked glycosylation
Smooth endoplasmic reticulum - steroid and lipid synthesis
what is the main function of the Golgi apparatus?
modifies, sorts and packages these molecules that are destined for cell secretion
the addition of mannose-6-ohosphate to proteins designates transport to lysosome
what is the main function of mitochondrion?
Aerobic respiration. Contains mitochondrial genome as circular DNA
what is the main function of the nucleus?
DNA maintenance
RNA transcription
RNA splicing - the process that removes the intervening, non-coding sequences of genes (introns) and joints the protein-coding sequences (exons)
what is the main function of a lysosome?
Breakdown of large molecules such as proteins and polysaccharides
what is the role of the nucleolus?
ribosome production
what is the role of ribosomes?
translation of RNA into proteins
what is the role of peroxisome
Catabolism of very long chain fatty acids and amino acids
Results in the formation of hydrogen peroxide
what is the role of proteasome?
Along with the lysosome pathway involved in degradation of protein molecules that have been tagged with ubiquitin
what is pulmonary surfactant?
a mixture of phospholipids, carbohydrates and proteins released by type 2 pneumocytes
The main functioning component is dipalmitoyl phosphatidylcholine (DPPC) which reduces alveolar surface tension.
how does pulmonary surfactant work?
as alveoli decrease in size, surfactant concentration is increased, helping prevent the alveoli from collapsing
reduces the muscular force needed to expand the lungs (i.e. decreases the work of breathing)
lowers the elastic recoil at low lung volumes and thus helps to prevent the alveoli from collapsing at the end of each expiration
what are the four main types of membrane receptors?
ligand-gated ion channels
tyrosine kinase receptors
guanylate cyclase receptors
G protein-coupled receptors
Ligand-gated ion channel receptors
generally mediate fast responses
e.g. nicotinic acetylcholine, GABA-A & GABA-C, glutamate receptors
Tyrosine kinase receptors
receptor tyrosine kinase: insulin, insulin-like growth factor (IGF), epidermal growth factor (EGF)
non-receptor tyrosine kinase: PIGG(L)ET: Prolactin, Immunomodulators (cytokines IL-2, Il-6, IFN), GH, G-CSF, Erythropoietin and Thromobopoietin
Guanylate cyclase receptors
contain intrinsic enzyme activity
e.g. atrial natriuretic factor, brain natriuretic peptide
G protein-coupled receptors
generally mediate slow transmission and affect metabolic processes
activated by a wide variety of extracellular signals e.g. Peptide hormones, biogenic amines (e.g. adrenaline), lipophilic hormones, light
7-helix membrane-spanning domains
consist of 3 main subunits: alpha, beta and gamma
the alpha subunit is linked to GDP.Ligand binding causes conformational changes to receptor, GDP is phosphorylated to GTP,and the alpha subunit is activated
G proteins are named according to the alpha subunit (Gs, Gi, Gq)
what are the subunits of G proteins?
Gs - Stimulates adenylate cyclase → increases cAMP → activates protein kinase A
Gi - Inhibits adenylate cyclase → decreases cAMP → inhibits protein kinase A
Gq - Activates phospholipase C → splits PIP2 to IP3 & DAG → activates protein kinase C
what are examples of Gs receptors?
- Beta-1 receptors (epinephrine, norepinephrine, dobutamine)
- Beta-2 receptors (epinephrine, salbuterol)
- H2 receptors (histamine)
- D1 receptors (dopamine)
- V2 receptors (vasopressin)
- Receptors for ACTH, LH, FSH, glucagon, PTH, calcitonin, prostaglandins
what are exampled of Gi receptors?
- M2 receptors (acetylcholine)
- Alpha-2 receptors (epinephrine, norephinephrine)
- D2 receptors (dopamine)
- GABA-B receptor
what are examples of Gq receptors?
- Alpha-1 receptors (epinephrine, norepinephrine)
- H1 receptors (histamine)
- V1 receptors (vasopressin)
- M1, M3 receptors (acetylcholine)
what are the causes of increased lung compliance?
age
emphysema - this is due to loss alveolar walls and associated elastic tissue
what are the causes of decreased lung compliance?
pulmonary oedema
pulmonary fibrosis
pneumonectomy
kyphosis
what is the mechanism of cardiac action potential
0- Rapid depolarisation- Rapid sodium influx
These channels automatically deactivate after a few ms
1- Early repolarisation - Efflux of potassium
2- Plateau- Slow influx of calcium
3- Final repolarisation - Efflux of potassium
4 - Restoration of ionic concentrations- Resting potential is restored by Na+/K+ ATPase
There is slow entry of Na+ into the cell decreasing the potential difference until the threshold potential is reached, triggering a new action potential
what is the most common cause of downs syndrome?
Nondisjunction - 94% of cases
other causes
Robertsonian translocation - (usually onto 14) - 5% of cases
Mosaicism 1%
what is skeletal muscle contraction dependant on?
Skeletal muscle contraction is dependent on acetylcholine which activates nicotinic acetylcholine receptors.
what are the major steps of muscle contraction?
- action potential reaches the neuromuscular junction, causing a calcium ion influx through voltage-gated calcium channels
- the calcium influx causes the release of acetylcholine into the extracellular space
the acetylcholine activates nicotinic acetylcholine receptors causing an influx of sodium, triggering an action potential - the action potential spreads through the T-tubules
the depolarization activates L-type voltage-dependent calcium channels (dihydropyridine receptors) in the T-tubule membrane, which are close to calcium-release channels (ryanodine receptors) in the adjacent sarcoplasmic reticulum
this causes the sarcoplasmic reticulum to release calcium - calcium binds to troponin C (found on actin-containing thin filaments) causing a conformational change, allowing tropomyosin to move, unblocking the binding sites
- myosin binds to the newly released binding site releasing ADP, pulling the Z bands towards each other
- ATP binds to myosin, releasing actin
what is the sarcomere?
basic unit of muscles that gives skeletal and cardiac muscle their stated appearance
where are calcium ions released from in response to depolarisation?
sarcoplasmic reticulum
what are the characteristics of type 1 muscle fibres?
slow contraction
red in colour due to presence of myoglobin
used for sustained force
uses triglycerides
high mitohcondiral density
what are the characteristics of type II muscle fibres?
fast contraction
white in colour due to absence of myoglobin
used for sudden movement
mainly fuels by ATP
low mitochondrial density
what is the mechanism of action of finasteride?
Finasteride is an inhibitor of 5 alpha-reductase, an enzyme which metabolises testosterone into dihydrotestosterone.
what are the indications for finasteride?
benign prostatic hyperplasia
male-pattern baldness
what are the adverse effects of finasteride?
Adverse effects
impotence
decrease libido
ejaculation disorders
gynaecomastia and breast tenderness
Finasteride causes decreased levels of serum prostate-specific antigen
when is glucose reabsorbed in the kidney?
The majority of glucose reabsorption in the nephron occurs within the proximal convoluted tubule
what cytokine is responsible for activating cells that primary form granuloma?
The cells that are being referred to here are macrophages, which are the primary constituents of granulomatous structures in diseases such as tuberculosis. Classically, macrophages are activated by Interferon-γ a
What is southern blotting used to do
detects DNA
what is northern blotting used to do
detects RNA
what is western blotting used to do
Detects proteins
Uses gel electrophoresis to separate native proteins by 3-D structure
Examples include the confirmatory HIV test
what is ELISA?
Enzyme-linked immunosorbent assay (ELISA)
> a type of biochemical assay used to detect antigens and antibodies
> a colour changing enzyme is attached to the antibody if looking for an antigen and to an antigen if looking for an antibody
> the sample therefore changes colour if the antigen or antibody is detected
> an example includes the initial HIV test
what nerve supply shoulder abduction?
Shoulder abduction - deltoid muscle - axillary nerve (C5,C6)
what nerve supplies elbow flexion?
Musculocutaneous nerve (C5-C7)
Elbow flexion (supplies biceps brachii) and supination
How is PCR carried out?
Initial prep
sample of DNA is added to the test tube along with two DNA primers
a thermostable DNA polymerase (Taq) is added
The following cycle then takes place
mixture is heated to almost boiling point causing denaturing (uncoiling) of DNA
mixture is then allowed to cool: complimentary strands of DNA pair up, as there is an excess of the primer sequences they pair with DNA preferentially
The above cycle is then repeated, with the amount of DNA doubling each time
Reverse transcriptase PCR
used to amplify RNA
RNA is converted to DNA by reverse transcriptase
gene expression in the form of mRNA (rather than the actually DNA sequence) can therefore be analyzed
what is homocystinuria?
Homocystinuria is a rare autosomal recessive disease caused by a deficiency of cystathionine beta synthase. This results in severe elevations in plasma and urine homocysteine concentrations.
what are the features of homocystinuria?
often patients have fine, fair hair
musculoskeletal
Marfanoid body habitus: arachnodactyly etc
osteoporosis
kyphosis
neurological: may have learning difficulties, seizures
ocular
downwards (inferonasal) dislocation of lens
severe myopia
increased risk of arterial and venous thromboembolism
also malar flush, livedo reticularis
what are the investigations for homocystinuria?
increased homocysteine levels in serum and urine
cyanide-nitroprusside test: also positive in cystinuria
what is the treatment for homocystinuria?
Treatment is vitamin B6 (pyridoxine) supplements.
what is riboflavin?
vitamin B2
Riboflavin is a cofactor of flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN) and is important in energy metabolism.
Consequences of riboflavin deficiency:
angular cheilitis
what is used to detected mutated oncogenes?
PCR
what statistical analysis is used for correlation?
Correlation
parametric (normally distributed): Pearson’s coefficient
non-parametric: Spearman’s coefficient
what are examples of second messengers?
Cyclic AMP (cAMP): Produced from ATP by the enzyme adenylate cyclase. It plays a vital role in signaling pathways, including those activated by hormones like adrenaline.
Cyclic GMP (cGMP): Derived from GTP, it is involved in signaling pathways related to vasodilation and smooth muscle relaxation.
Calcium Ions (Ca²⁺): Act as a second messenger in various signaling pathways, influencing muscle contraction, neurotransmitter release, and many other processes.
Inositol Triphosphate (IP3): Generated from phosphatidylinositol 4,5-bisphosphate (PIP2) by phospholipase C, it plays a key role in increasing intracellular calcium levels.
Diacylglycerol (DAG): Also produced from PIP2, it activates protein kinase C and is involved in various cellular functions.
which phase of the cell cycle determines cell cycle length
G1 phase determines cell cycle length
The G1 phase is the initial growth phase of the cell. It is under the influence of p53. Through the action of several different regulatory proteins, it determines the overall length of the cell cycle. Different cells in different tissues have variable cell cycle lengths e.g. skin cells replicate more quickly than hepatocytes.
what is the nerve root of the radial nerve?
In the axilla: lies posterior to the axillary artery on subscapularis, latissimus dorsi and teres major.
Enters the arm between the brachial artery and the long head of triceps (medial to humerus).
Spirals around the posterior surface of the humerus in the groove for the radial nerve.
At the distal third of the lateral border of the humerus it then pierces the intermuscular septum and descends in front of the lateral epicondyle.
At the lateral epicondyle it lies deeply between brachialis and brachioradialis where it then divides into a superficial and deep terminal branch.
Deep branch crosses the supinator to become the posterior interosseous nerve.
what is are the root values of the radial nerve?
C5-T1
what are the patterns of damage of the radial nerve?
wrist drop
sensory loss to small area between the dorsal aspect of the 1st and 2nd metacarpals
what i
what is scurvy and what are the symptoms
vitamin C deficiency
Follicular hyperkeratosis and perifollicular haemorrhage
Ecchymosis, easy bruising
Poor wound healing
Gingivitis with bleeding and receding gums
Sjogren’s syndrome
Arthralgia
Oedema
Impaired wound healing
Generalised symptoms such as weakness, malaise, anorexia and depression
