Pathology and Physiology Flashcards
In the bladder, the first urge to void is felt at, and a marked sense of fullness is at ?
150mls and 400mls
What is permeable in the thin descending portion of the loop of Henle?
Highly permeable to H2O and only slightly permeable to NACL
Due to the presence of aquaporin-1 in both the apical and basolateral membrane
What is permeable in the thin ascending portion of the loop of Henle
Not permeable to H2O
Highly permeable to NaCl
What is permeable in the thick ascending portion of the loop of Henle
Not permeable to H2O
Only slightly permeable to NaCl
What is permeable in the collecting tubules of the kidneys?
highly permeable to water in the presence of vasopressin
How is sodium transported in the renal tubule
Actively transported out of all parts of the renal tubule except the thin portions of the loop of Henle
Filtration fraction of Kidney is?
0.16-0.20
Explain the control of the external urethral sphincter
Controlled by the pudendal nerves which are somatic
Contraction of the perineal muscles and external sphincter can be contracted voluntarily, preventing urine from passing down the urethra or interrupting flow once urination has begun
What happens to the kidneys during a fall in systemic blood pressure?
Renal plasma flow decreases more than eGFR
Filtration fraction increases
Both afferent and efferent arterioles are constricted, efferents to a greater degree
Sodium retention is marked
Nitrogenous products of metabolism are retained in the blood giving rise to azotaemia and uraemia
Prolonged can cause renal tubular damage and acute renal failure
Osmolality of the pyramidal papilla
1200mosm/kg
What is the best substance to measure eGFR?
Eg, Inulin
a substance that is freely filtered, niether reabsorbed nor secreted, is nontoxic and not metabolised by the body
Proximal convoluted tubule reabsorbs how much filtered sodium ?
60%
How does sodium move through the nephron?
PCT reabsorbs 60% of filtered sodium
It is pumped back into the interstitium by the Na/K/ATPase
It does share a common carrier with glucose
30% is absorbed via the Na/2Cl/K cotransporter in the thick ascending limb of the loop of Henle
7% via the NaCL contransporter in the DCT
3% via the ENaC channels in the collecting duct
In osmotic diuresis what causes increased urine flow?
Decreased water reabsorption in the PCTs and loop of Henle
Renal acid secretion is altered by?
Changes in the intracellular pCO2
Potassium concentration
Carbonic anhydrase level
adrenocorticol hormone concentration including aldosterone
Describe glucose absorption in the kidneys?
Glucose reabsorption is an active process
Closely associated with sodium
Occurs predominantly in the proximal convoluted tubule
Sodium Glucose Linked Transporters actively reabsorb glucose (SGLT)
excreted in urine if renal threshold is exceeded
Urea in the kidneys
Passively crosses biological membranes, permeability is low because of its low solubility in lipid bilayer
Urea transporters (4) move urea by facilitated diffusion out of the proximal tubule.
Urea plays a role in the establishment of an osmotic gradient in the medullary pyramids.
Increases the ability of the kidney to concentrate urine in the collecting ducts .
Where in the kidney is the tubular fluid isotonic?
Proximal convoluted tubule
In the PCT water moves passively out of the tubule along the osmotic gradient.
Conditions that increase renin secretion
Sodium depletion, diuretics, hypotension, haemorrhage, upright posture, dehydration, cardiac failure, cirrhosis, constriction of renal artery or aorta
Factors that inhibit renin secretion
Increased Na and Cl reabsorption across macula densa
Increased afferent arteriolar pressure
Angiotensin II
Vasopressin
Describe the cells that make up the proximal convoluted tubule?
Made up of a single layer of cells that interdigitate with one another and are united by apical tight junctions
Luminal edges of the cells had a striate brush border due to microvilli
Describe the renal handling of potassium?
Potassium (K) is actively reabsorbed in the proximal convoluted tubule
K is secreted in the distal tubular cells
In the collecting ducts K is secreted
The rate of K secretion is proportionate to the rate of flow of the tubular fluid through the distal portions of the nephron, because with rapid flow there is less opportunity for the tubular K concentration to rise to a value that stops further secretion
Describe Vasopressin
AKA Antidiuretic Hormone
Released from posterior pituitary
Increases the permeability of the collecting ducts so that water enters the hypertonic interstitium of the renal pyramids.
urine becomes concentrated and volume decreases.
standing increases vasopression secretion
There are 3 vasopressin receptos V1a, V1b, V2
Describe the Proximal Convoluted Tubule
15mm long
55um in diameter
wall is made up of single cell layer, united by tight apical junctions.
Luminal edges have a brush border due to microvilli
Found in the cortex of the kidney
Action of aldosterone on the kidneys
Promotes sodium reabsorption and potassium secretion
6 ways aldosterone promotes Na and water retention and lowers K conc
- Acting on the distal tubule and collecting duct of the kidney nephron, it activates the basolateral Na/K pumps, which pumps three sodium ions out of the cell and two potassium ions into the cell.
- Aldosterone upregulates epithelial sodium channels increasing apical membrane permeability for Na+.
- Chloride is reabsorbed in conjunction with sodium cations to maintain the system’s electrochemical balance.
- Aldosterone stimulates the secretion of K+ into the tubular lumen
- Aldosterone stimulates Na+ and water reabsorption from the gut, salivary and sweat glands in exchange for K+.
- Aldosterone stimulates secretion of H+ in exchange for Na+ in the intercalated cells of the cortical collecting tubules regulating plasma bicarbonate levels and acid/base balance
Neurological pathways involved in normal micturition
Sacral spinal reflex mediated by S2 S3 and S4 nerve roots
First urge to void at 150mls, marked fullness at 400mls
Micturition reflex
Sympathetic nerves to the bladder play no role in micturition
What is the micturition reflex?
Stretch receptor in the bladder wall
Afferent limb in pelvic nerves
parasympathetic efferent fibres, via same pelvic nerves, mediate contraction of detrusor muscle.
Pudendal nerve S2 S3 S4 permits voluntary contraction of perineal muscles/external urethral sphincter to slow or halt flow
Describe the muscles involved in micturition
Bladder; smooth muscle arranged in spiral, longitudinal and circular bundles
Circular bundle is called the detrusor muscle, contraction is responsible for involuntary emptying
External urethral sphincter; skeletal muscle, relaxes during micturition, voluntary controlled
Perineal muscles, relax during micturition, voluntarily controlled.
Contraction of abdomen aids expulsion of urine.
Factors that stimulate micturition
Stretch/pressure
Higher centre input
Parasympathetics
sympathetic inhibiting drugs
Inhibitors of micturition
Parasympathetic inhibitors
Higher centres
Sympathomimetics
Consequences of glycosuria
Osmotic diuresis
dehydration
electrolyte loss
Where does sodium reabsorption occur in the nephron?
Filtered by the glomerulus, 99% reabsorbed overall
60% reabsorbed in the PCT by the Na/H exchange and a range of cotransportes with gluose
30% thick ascending limb of the loop of henle
7% DCT via NaCl cotransporter
3% via ENaC channels in the collecting ducts
With high Na intake, what mechanisms enhance Na excretions
Stretch receptors in pulmonary veins inhibit sympathetic outflow of the kidneys and decreased Na absorption
Small increase in arterial pressure can cause pressure natiuresis
Suppression of ATII formation, reducing aldosterone activity
Stimulation of ANP
How does the kidney reduce na secretion
Reducing eGFR to reduce the amount filtered
Increasing tubular reabsorption via increase in adrenocorticol hormones such as aldosterone
How does aldosterone influence sodium handling?
Aldosterone acts on principal cells in collecting ducts to increase the number of active epithelial sodium channls
Upregulates and activated basolateral Na/K ATPase
Increased tubular reabsorption of Na and Cl follows
Secretion of K into lumen via exchange with Na
Latent period of 10-30 minutes before the effect
Microscopic changes in Malignant Hypertension
Intimal thickening caused by concentric proliferation of smooth muscle cells and collagen which accumulates in a layered configuration (together with accumulation of proteoglycans and plasma proteins).
This gives an onion skinning appearance.
This lesion is also called hyperplastic arteriolitis and correlates with renal failure in malignant hypertension
Describe post infections glomerulonephritis
Acute glomerulonephritis occurs most frequently in children aged 6-10yrs, 1-4 weeks after a streptococcal infection of the pharynx or skin (impetigo). It is due to a group A beta haemolytic streptococcus
Manifestations of nephrotic syndrome
massive proteinuria, hypoalbuminaemia, generalised oedema (increased interstitial fluid), hyperlipidaemia and lipiduria
Causes of nephrotoxic acute tubular necrosis
Gentamicin
Radiographic contrast agents
Heavy metal poisoning
Organic solvents
Most common cause of acute renal failure
Acute tubular necrosis in 50%
Describe ischaemic acute tubular necrosis (ATN)
Associated with focal tubular epithelial necrosis.
There is rupture of the basement membrane and occlusion of tubular lumen by casts.
Lesions occur in a skip like pattern along the nephron.
The straight portion of the proximal tubule (PST) and the ascending thick limb in the renal medulla are especially vulnerable.
What are the extra renal congenital abnormalities in polycystic kidney disease
40% have polycystic liver disease. Intracranial berry aneurysms arise in the circle of Willis and Sub-arachnoid Haemorrhage (SAH) account for 4-10% of individuals.
Mitral valve prolapse and other cardiac valvular anomalies occur in 20-25%. Ultimately about 40% of adult patients die of coronary or hypertensive heart disease, 25% of infection, 15% of ruptured berry aneurysms or hypertensive intracerebral bleed.
What is the most common cause of chronic pyelonephritis?
Chronic vesicoureteral reflux
How does the kidney deal with potassium
Freely filtered at the glomerulus 600mmol/day
Actively reabsorbed in the PCT over 90%
Also reabsorbed in the Na/K/2Cl co transporter
Secreted in the DCT - rate proportional to flow
Secreted in the CD in response to aldosterone
Where in the renal tubules does the intratubular and interstitial osmolality hold the same values?
Thin descending loop of Henle
Where does acidification of the urine occur
Proximal and distal tubules and collecting ducts
How is H+ secreted in the PCT and the DCT/CD?
PCT: Na/H exchange transporter, this pathway also involves the action of carbonic anhydrase which allows the recycling of H+ and absorption of 1Na and 1HCO3 for every H+ secreted
DCT/CD: secretion of H+ is independent of Na. ATP driven pump, also H/K/ATPase pump and anion exchanger
What is the limiting pH of urine and where does it occur
pH is 4.5
Occurs in the collecting duct
In metabolic acidosis describe the buffer systems
Bicarbonate - HCO3 forms CO2 and H2O
Phosphate - HPO4 forms H2PO4
Ammonia - NH3 to NH4
What happens to glutamine synthesis in chronic metabolic acidosis
Glutamine synthesis increased in the liver
Provide the kidneys with enough ammonia to form a buffer
How do the kidneys deal with potassium ?
Freely filtered at the glomerulus 600mmol/day
Actively reabsorbed in the PCT
Reabsorbed in the NaK2Cl co transporter
Secreted in the DCT
Secreted in the CD in response to aldosterone
Explain potassium transport in the collecting duct
The H-K ATPase in the cells of the collecting ducts reabsorbs K in exchange for H
What is the role of urea in the countercurrent mechanism
Contributes to the osmotic gradient in the medullary pyramids
Enhances the ability of the kidney to concentrate urine
How does the kidney handle urea?
Facilitated diffusion out of the late PCT
Secreted in the loop of henle
Reabsorbed in the collecting ducts
40% of filtered urea can be found in urine
The amount of urea depends on the amount filtered which is influenced by dietary protein
How does urea reach the interstitium ?
Facilitated diffusion
Transported via 4 different urea transporters
What is normal renal blood flow?
1.2-1.3L per minute or 25% of cardiac output
What factors determine renal blood flow?
Precision pressure (systemic MAP)
Renal artery effects - local constriction from Na, Ang II, dilation from ACh, PGs, dopamine, renal nerves, auto regulation, regional differences between cortex and medulla
How can renal blood flow be measured
- Fick principle - amount of a substance taken up per unit time divided by arterio-venous concentration difference
- Para-amino hippuric acid (PAH) - excreted 90% cleared
ERPF = clearance of PAH = UV/P = 630ml/min
U = urine concentration
V = volume of urine collected in minutes
P = plasma concentration - Acute renal plasma flow = ERPF/0.9 = 700ml/min
- Renal blood flow (including RBC) so it’s
Acute renal plasma flow / 1-HCT = 1250ml/min
How do blood flow and oxygen extraction vary in different parts of the kidney?
Cortical flow is high and oxygen extraction is low
Medullary blood flow is low and oxygen extraction is high because there is a lot of metabolic work done
Medulla is more vulnerable to hypoxia damage
What is a normal GFR
125ml/minute or 180L in 24 hours
How does thirst restore fluid status?
As plasma oncotic pressure rises it is sensed by the osmoreceptors in the anterior hypothalamus
Triggers a release of vasopressin from the posterior pituitary
Vasopressin acts on the V2 receptor to trigger insertion of aquaporin channels into the luminal membrane of the renal collecting tubules. Aquaporins are usually stored in the cytoplasm of principal cells. Insertion of these allows more water to return to the body
How does hypotension activate the RAAS system
Hypotension leads to reduced perfusion pressure of the afferent glomerular arteriole
Stimulating release of renin by the juxtaglomerular cells
Renin converts angiotensinogen to angiotensin I
Angiotensin converting enzyme converts angiotensin I to II
Angiotensin II acts on the adrenal cortex’s zona glomerulosa cells to release aldosterone
This acts on the renal distal tubules to retain Na+ and water thus increase intravascular volume
Angiotensin II is also a potent arteriolar constrictor
Physiological factors are involved in regulating renin secretion
Intrarenal baroreceptors - an increase in afferent arteriolar pressure in JG cells causing a decrease in renin secretion
Increased resorption of Na and Cl in the distal tubules in the macula densa causes a decrease in renin secretion
Increase in sympathetic nervous system stimulates renin
Vasopressin can decrease renin
Angiotensin II provides inhibitory feedback to JG cells
What is the main inhibitory neurotransmitter of the spinal cord?
Glycine
It is also the responsible for direct inhibition in the brainstem
What is the main inhibitory neurotransmitter in the brain?
GABA
Describe the vestibulocochlear nerve?
CNVII
special senses for hearing, equilibrium and motion
originate in the grooves of the pons and medulla
run through the internal acoustic meatus
vestibular nucleus arises in the pons
Where is visual acuity the greatest?
Fovea centralis
Principal hypothalamic regulatory mechanisms?
Temperature regulation
Neuroendocrine control
‘Appetite’ behaviour - thirst hunger sexual
Defensive reactions - fear, rage
Control body rhythms
What is the kappa receptor responsible for?
analgesia, diuresis, sedation, miosis, slow GIT transit, dysphori, psychotomimetic effects
What are the Mu receptors responsible for?
analgesia, respiratory depression, constipation, euphoria, sedation, miosis and modulation of hormone and neurotransmitter release
What are Delta receptors responsible for?
analgesia and modulation of hormone and neurotransmitter release
Which most easily penetrates CSF - CO2, H2O, N2O or O2?
CO2 - linked with strict ventilation control
water Co2 and O2 penetrate the brain with ease
Describe the Fovea Centralis
The pit in the macular part of the retina which allows for maximum acuity of vision.
It is a thin portion of the retina free of rods.
It has densely packed cones.
Provides a direct pathway to the brain.
Few overlying cells and no blood vessels.
What is the main excitatory transmitter in the brain and spinal cord?
Glutamate.
Aspartate is also excitatory
The sensation for cold is transmitted by?
the lateral spinothalamic tracts
is a crossed sensorimodality
mediated by typa A delta fibres
relayed by the thalamus
what doe the lateral spinothalamic tracts transmit?
pain and temperature
what do the anterior/ventral spinothalamic tracts transmit?
crude touch and pressure
What do the dorsal columns transmit?
fine touch, two point discrimination, proprioception, vibration sense
Roles of alpha 1 receptors
Eyes - mydriasis
Skin & splanchnic vessels – constriction
Skeletal muscle - constriction / dilation
Bronchial glands - increase secretion
GIT motility & tone - decreased - contraction of GIT sphincters
Contraction of urinary sphincter
Contraction of pregnant uterus
Ejaculation in male
Skin pilomotor muscles - contraction
Liver - glycogenolysis - pancreas acini - decrease secretion
Salivary glands - thick, viscous secretion
What will happen with a dissection of the lateral spinal cord?
Loss of voluntary motor function on same side
Will damage the lateral corticospinal tract, which decussates in the pyramids, resulting in loss of cortical control of motor function on the ipsilateral side, causing ipsilateral hyperreflexia
What does monamine oxidase breakdown?
MOA - A breaks down;
serotonin
melatonin
noraderenaline
adrenaline
dopamine
MOA - B breaks down;
Phenethylamine
benzylamine
Both;
dopamine
tyramine
trypatmine
Formation of adrenaline
Phenylalanine is converted to Tyrosine
Tyrosine to L-Dopa by tyrosine hydroxylase
L-Dopa to Dopamine by DOPA decarboxylase
Dopamine to noradrenaline by dopamine Beta hydroxylase
Noradrenaline to adrenaline by PNMT.
Formation of serotonin
Tryptophan to 5-HTP by tryptophan hydroxylase
5-HTP to sertonin by Dopa decarboxylase
Serotonin broken down by MAO to 5-HIAA
Describe acetylchoinesterase?
Breaksdown acetylcholine by hydrolysis to ACh to choline and acetate in the synaptic cleft.
Inhibitory neurotransmitters increase the post synaptic conductance of which of the following; Chloride, sodium, calcium, magnesium?
Chloride
Chloride conductance is important to both GABA and glycine functioning as inhibitory neurotransmitters
Describe CSF?
CSF is 150mls, production of 550ml/day
CSF turnover is 3.7 times a day.
50-70% of CSF is formed in the choroid plexuses.
Absorbed through the arachnoid villi into veins, mainly the cerebral venous sinus.
Has the same composition as cerebral extracellular fluid.
Has higher concentration of Mg than plasma.
Has lower concentration of Ca than plasma.
Osmolility is the same as plasma.
Describe Excitatory Postsynaptic Potentials (EPSP)?
Produced by depolarization of the postsynaptic cell membrane immediately under the presynaptic ending.
Excitatory transmitter opens Na and Ca channels in the post synaptic membrane.
The area of current flow is so small and does not drain enough positive charge to depolarize the whole membrane.
An EPSP is created in one synaptic knob.
Activity in more than one synaptic knob creates spatial summation.
Repeated afferent stimuli causes new EPSPs before old ones decay.
Response of EPSPs is proportionate in size to strength of the afferent stimuli.
What cells create myelin in the CNS and what cells in the PNS?
Oligodendrocytes in CNS
Schwann cells in the PNS
Local anaesthetics work most strongly on which fibres?
Type C (then type B, then type A)
Describe Polio
Polio invades the CNS and replicates in the motor neurons of the spinal cord and brainstem.
Commonly the anterior horn motor neurons.
The posterior horns of the spinal cord and the cranial motor nuclei are sometimes involved.
Does not involve the dorsal root ganglion.
What is the order of the structures conveying visual sensation?
Optive nerve
Optic Chiasm
Optic tract
Lateral geniculate body
Occipital cortex
Describe the ciliary muscle
smooth muscle responsible for lens accomodation
contained within the ciliary body
contraction of the ciliary muscle enables the lens to focus light onto the retina by changing its shape
what lesion causes loss of peripheral vision or macular sparing
occipital lesion
Describe meningiomas
Meningiomas are predominantly benign tumours of adults, usually attached to the dura, that arise from the meningothelial cell of the arachnoid.
They are slow growing lesions.
They are uncommon in children and generally show a female predominance (3:2).
Meningiomas often express progesterone receptors and may grow more rapidly during pregnancy
Describe MS
MS is an autoimmune demyelinating disorder characterised by distinct episodes of neurological deficits, separated in time, attributable to white matter lesions that are separated in space.
It is the most common of the demyelinating disorders.
Women are affected twice as often as men.
Onset in children or after the age of 50yr is rare.
The frequency of relapses tend to decrease during the course of time, but there are steady neurologic deterioration in most affected individuals.
CSF has a mildly elevated protein level and in one third of cases there is moderate pleocytosis.
IgG levels are increased and oligoclonal bands are usually observed on immunoelectrophoresis
Describe Rabies
Rabies is a severe encephalitis transmitted to humans by the bite of a rabid animal-usually a dog or various wild animals. Exposure to certain species of bats, even without a known bite, can also lead to rabies.
Negri bodies, the pathognomonic microscopic finding, are cytoplasmic, round to oval, eosinophilic inclusions that can be found in pyramidal neurons of the hippocampus and Purkinje cells of the cerebellum, sites usually devoid of inflammation.
Since the virus enters the CNS by ascending along the peripheral nerves from the wound site, the incubation period (1-3months) depends on the distance between the wound and the brain.
The disease begins with non specific symptoms of malaise, headache, and fever, but the conjunction of these symptoms with local paraesthesia around the wound is diagnostic.
Describe atraumatic intracerebral haemorrhage?
Occurs in middle to late adult life, peak incidence 60yrs.
The 2 main aetiologies are hypertension and cerebral amyloid angiopathy (CAA).
Other local or systemic factors may cause or contribute: coagulation disorders, neoplasms, vaculitis, aneurysms and vascular malformations.
Hypertension accounts of >50% of clinically significant haemorrhages and for 15% of deaths in patients with chronic hypertension.
These haemorrhages occur in the putamen (50-60%), thalamus, pons and cerebellar hemispheres.
CAA bleeds are often restricted to the leptomenigeal and cerebral cortical arterioles and capillaries
Describe retinoblastomas?
Retinoblastoma is the most common primary intraocular malignancy of children.
Cell of origin is neuronal.
Approximately 40% of cases occur in patients who inherit a germline mutation of one RB allele.
Chemotherapy is often the first of treatment to attempt to reduce the tumour followed by laser treatment or cryopexy.
Spread is to the brain and bone marrow and seldom to the lungs.
Prognosis is poor if there is extra ocular extension and invasion along the optic nerve, and by choroidal invasion
What metabolite accumulates in stroke propagating cellular damaging?
Glutamate
Ischaemia leads to ATP depletion in stroke by multiple mechanisms, one which releases glutamate. This causes cell damage via calcium influx through NMDA-type glutamate receptors
What is the most important ion for cardiac resting membrane potential?
Potassium
What is calmodulin?
Calmodulin is involved in smooth muscle contraction, synaptic function, protein synthesis, activating calcium channels and t cells, and activating phosphorylase.
What does calmodulin do to smooth muscle?
Ca binds to calmodulin, and the resulting complex activates calmodulin-dependent myosin light chain kinase.
This enzyme catalyses the phosphorylation of the myosin light chain in serine at position 19, increasing its ATPase activity,
leading to smooth muscle contraction.
Describe resting nerve membrane potential
usually -70mV in the cell
Na is actively transported out of neurons
K is actively transported in
K channels maintain the resting membrane potential
For excitable tissue, changes in external potassium will affect?
the resting membrane potential.
Causes hyperpolarisation
hyperkalaemia decreases resting membrane potential making it more negative
For excitable tissue changes in external Na affects?
the strength of the action potential
What is bradykinin?
Bradykinin is a potent endothelium-dependent vasodilator which leads to hypotension, causes contraction of non-vascular smooth muscle, increases vascular permeability and also is involved in the mechanism of pain.
Bradykinin also causes natriuresis, contributing to an even more drop in blood pressure. There is an acceleration of the heart rate
It is broken down by ACE
initiation of smooth muscle contraction is due to ?
Calcium influx
via voltage gated and ligand gated Ca channels
with fibre type A, what is the function of alpha?
proprioception, motor (somatic)
with fibre type A, what is the function of beta?
touch (long hairs), pressure
with fibre type A, what function is gamma?
motor (muscle spindles)
with fibre type A, what function is delta?
pain, cold, tough (small hairs)
what function is fibre type B?
preganglionic autonomic
with regards to fibre type C, what function is dorsal root?
Pain, temperature, mechanoreceptor, reflex responses
with regards to fibre type C, what is the function of the sympathetic type?
postganglionic synatpic
Which nerve fibres are most susceptible to hypoxia?
Fibre type B ( then A then C)
Which nerve fibres are most susceptible to pressure?
Type A (then B then C)
Morphology of Cardiac muscle cells
Cardiac muscle striations are similar to skeletal muscle
Z lines are present
Muscle fibres branch and interdigitate
Intercalated discs - strong unions between fibres, extensive series of folds at the Z line
Gap junctions - along the side of the muscle fibres next to the disks, provide low resistance bridges for the spread of excitation
Contractile mechanism in skeletal muscle depends on what 4 proteins?
Myosin II
Actin
Tropomysin
Toponin (T, I, C )
In skeletal muscle what are the thick filaments?
made of myosin II
have two heads and a long tail
Heads form cross links to actin
contain an actin biding site and a catalytic site that hydrolyses ATP
In skeletal muscle what are thin filaments?
Two chains of Actin that form a double helix
Tropomyosin forms long filaments located in the groove between the two chains
Troponin are small globular units located in intervals
What do the three types of Troponin do in skeletal muscle?
Troponin T - binds the other troponin components to tropomyosin
Troponin I - inhibits the interactions of myosin with actin
Troponin C - contains the binding sites for the Ca that initiates contraction
In a sarcomere what is the I band?
The pale band containing the z disk plus the areas actin actin filaments not overlapping with myosin filaments
Becomes shorter during contraction as overlap increases
In a sarcomere what is the A band?
the dark band which extends the length of the myosin filament
never changes length
In a sarcomere what is the H zone?
the area of myosin filaments not overlapping with actin filaments
becomes shorter during contraction as overlap increases
In a sarcomere what is the M line?
dark staining line where myosin filaments are anchored to one another in the centre of the sarcomere
what does Na/K/ATPase do to Na and K?
3Na out from the cell
2K into the cell
visceral smooth muscle is characterised by?
Instability of its membrane potential
continuous irregular contractions = maintained partial contraction = tonus
what is the resting potential of cardiac muscle cell (non pacemaker)
-90mV
what happens to visceral smooth muscle when it is stretched?
it contracts
Describe type II muscle fibres
Type II muscle fibres- Fast; glycolytic; white.
Myosin isoenzyme ATPase rate= fast
Calcium pumping capacity of sarcoplasmic reticulum=High
Diameter= large
Glycolytic capacity= high
Oxidative capacity= Low
Describe cAMP
cAMP is an important secondary mechanism.
It is also known as 3’,5’-monophosphate.
It is formed from ATP by the action of adenylyl cyclase enzyme.
cAMP is then converted to the physiological inactive 5’AMP by phosphodiesterase.
cAMP activates protein kinase A that catalyses the phosphorylation of proteins
where is B12 absorbed
in the ileum
In the intracellular fluid what is the most prevelant cation and anion
cation is K+
anion is Protein -
Describe protein digestion
begins in the stomach
absorption takes place rapidly in the duodenum and jejunum
at least 7 different transport systems are required for absorption
Pepsinogen I is found only in the acid secreting regions of the stomach. Pepsinogen II is also found in the pyloric region.
Describe fat absorption
Most fat digestion begins in the duodenum
pancreatic lipase being one of the most important enzymes
Describe iron absorption
Regulated by recent dietary intake, iron stores and level of erythropoeisis in bone marrow
Almost all is absorbed in the duodenum
Is increased by Vitamin C
28-year-old woman is found to have megaloblastic anaemia. She reports tingling of her hands bilaterally. She is likely deficient in a vitamin absorbed in which part of the gastrointestinal tract?
Ileum
B12 deficency
Where are Baroreceptors located?
Carotid sinus, aortic arch, walls of right and left atria, entrance of superior and inferior vena cava, pulmonary veins and circulation
What does gastrin do?
Gastrin stimulates gastric acid secretion, increases gastric motility, and increases pancreatic and biliary secretions.
What is the Poiseuille-Hagen Formula?
Q = (P1-P2) x [pie x r4] x 1/8nl or
Flow = [(Pressure difference) x pie x r^4/ [viscosity x 8 x L]
P = pressure difference between two ends of the tube
n = viscosity
r = radius
L = length of tube
Q = flow
What is flow?
proportionate to pressure difference at 2 ends of a tube
what is endothelium derived relaxing factor?
also known as NO
How does radius alter resistance?
change in radius alters resistance to the 4th power
therefore a 2 fold increase in radius decreases resistance by a factor of 16
what contributes to venous blood flow?
the pumping of the heart
skeletal muscle contraction
intrathoracic pressure variations
the ‘c’ wave of the jugular pulse is due to ?
transmitted pressure due to tricuspid bulging in isovolumetric contraction
the a wave of the jugular pulse is due to ?
due to atrial systole, rise in venous pressure
the v wave of the jugular pulse is due to ?
the v wave mirrors the rise in atrial pressure before the tricuspid wave opns during diastole
what stimulates endothelin 1?
angiotensin II
catecholamines
GF
hypoxia
insulin
oxidised LDL
HDL
shear stress
thrombin
what inhibits Endothelin 1?
NO, ANP, PGE2, prostacyclin
Constriction of arterioles?
Local factors: Decreased local temperature, autoregulation
Endothelial products: Endothelin 1, locally released platelet serotonin
Circulating hormones: Epinephrine- EXCEPT in skeletal muscle and liver, noradrenaline, AVP, angiotensin II, Circulating Na-K ATPase and neuropeptide Y
Neural factors: Increased discharge of sympathetic nerves
Dilation of arterioles?
Local factors: Increased CO2, K, adenosine, lactate and local temperature. Decreased O2 and local pH.
Endothelial products: NO, kinins and prostacyclin.
Circulating hormones: Epinephrine in skeletal muscle and liver, CGRP alpha, substance P, histamine, ANP and VIP.
Neural factors: Decreased discharge of sympathetic nerves and activation of sympathetic cholinergic vasodilator nerves to skeletal muscle.
Phases of the valsalva manouvre
Phase 1: Onset of straining and the beginning of an increase in intrathoracic pressure.
Phase 2: The persistent straining and maintenance of the increased intrathoracic pressure.
Phase 3: Release of breath-holding and glottic pressure with a sudden drop in the intrathoracic pressure.
Phase 4: shortly after release of straining, Sudden increase in cardiac output and aortic pressure which stimulates the baroreceptors causing a bradycardia
Describe peripheral chemoreceptors
they are in the carotid and aortic bodies
primarily activated by reduction in paO2 and pH
respond to increase in paCO2
they are responsible for all the increase of ventilation
What is the variation of the pressure in the capillaries?
in nail bed is 32mmHg at the arteriolar end
15mmHg at the venous end
but also ?5mmHg at arterolar end and 0 at venous end
Describe the blood in the capillaries
blood moves slowly
transit time from arteriolar end to venous is 1-2 seconds
5% of circulating blood is in capillaries
the only part where O2 and nutrients can enter the interstitial fluid and CO2 removed
Where are chemoreceptors located
in the carotid body at the bifurcation of the common carotid artery and the aortic arch
Mechanisms of heat loss at 21 degrees celsius
70%: radiation and conduction
27%: vaporization of sweat
2%: respiration
1%: urination and defecation
what % of ATP is used for different processes?
27% is used for protein synthesis,
24% for Na/K/ATPase to help set membrane potential
9% by gluconeogenesis
6% by Ca2+ ATPase to maintain a low cytosolic Ca2+ concentration
5% by myosin ATPase
3% by ureagenesis.
to diagnose SIADH what plasma and urine values do you need?
Euvolaemic hyponatraemia <135mmol/L
Plasma osmolality <280mOsm/L
Urine osmolality >100mOsm/L
Urine sodium >20mmol
Urine osmolality>serum osmolality
Causes of SIADH
malignancy, CNS, lung infections and granulomatous disease
psychoactive drugs-MAOI, SSRI, TCI, NSAIDS, chlorpromazine and chemotherapeutic drugs
Regarding blood buffers, what is the HCO3:H2CO3 ratio at a PH of 7.4?
pH = pka + log HCO3/H2CO3
7.4 = 6.1 + log HCO3/H2CO3
1.3 = log HCO3/H2CO3
which somehow = log 20 =1.3?
pH7.4=20
pH6.0=0.9
pH7.1=10
pH7.3=16
Regarding fluid composition what % of body weight is ICF
40%
How do you calculate the anion gap?
(Na+ + K+) – (Cl- + HCO3-) = Anion Gap
What can cause an anion gap metabolic acidosis?
Methanol, metformin, uraemia, renal failure, ketoacids, lactic acids, ethanol, salicylates, ethylene glycol, paraldehyde, toluene, iron and cyanide.
What is the principe interstitial buffer ?
carbonic acid-bicarbonate system (CA-B). The CA-B system will function without the carbonic anhydrase enzyme
In chronic acidosis, the major adaptive buffering system in the urine is
Ammonium NH4
(ammonia) NH3 + H = NH4
What is the major buffer in interstitial fluid?
Bicarbonate
What is the major buffer in intracellular fluid?
Phosphate
Describe Vitamin D metabolism
Vitamin D3 is produced in the skin from 7-dehydrocholesterol by action of sunlight.
Metabolised by p450
25-hydroxilation occurs in the liver, converting vitamin D3 into 25-hydroxycholecalciferol
in the kidney this is converted to 1,25 dihydroxycholecalciferol and less active 24,25 duhydroxycholecacliferol
where is platelet activating factor produced?
by neutrophils, basophils, platelets and endothelial cells
Define hypertrophy
increase size of cells and so increase size of the organ. No new cells
The phenotype of an individual cell me be altered in hypertrophy
What is dystrophic calcification
In area of necrosis of any type
Inevitable in atheromas of advanced atherosclerosis
Define apoptosis
a pathway of cell death when cells activate enzymes that degrade the cells own nuclear DNA and proteins.
Fragments break off that are targets for phagocytes.
does not illicit an inflammatory response
Define metaplasia
a reversible change when cell type is replaced by another
eg squamous to columnar in Barrots
what are the two main process of necrosis
- Denaturation of intracellular proteins, coagulative necrosis (with initial maintenance of basic cell structure)
- Enzyme digestion of organelles, liquefactive necrosis
morphological features of necrosis
Eosinophilic (pink) cells due to loss of RNA mediated basophilia
Myelin figures - phospholipid masses that can replace cells when they necrose
Fragmented membranes
Nuclear changes
Autolysis - intrinsic cell digestion
Heterolysis - digestion by lysosomal enzymes of immigrant leukocytes
2 main characteristics of apoptosis
Chromatic condensation and DNA fragmentation
what happens when ATP is depleted 5-10%
- NaKATPase fails, raise in intracellular Na, loss of K = cell swelling
- Increased AMP stimulate anaerobic metabolism
- Ca Mg ATPas fails, increasing intracellular Ca
- Detachment of ribosomes causing reduced protein synthesis
- Misfolding of proteins due to deprivation of O2and glucose - unfolded protein response
What happens to a cell with loss of calcium homeostasis
Increase Ca activates phospholipidases, proteases, ATPases and endonucleases
How are oxygen derived free radicals initiated ?
Radiation
exogenous chemicals
reduction-oxidation reactions in metabolism
transition metal reactions
NO
What effect do free radicals have on a cell
Phospholipid membrane breakdown through lipid preoxidation
Oxidative modification of proteins result in fragment proteins
DNA lesions as free radicals react with nucleobase thymine, produce single stranded breaks in DNA
Cellular mechanisms to remove free radicals
- Antioxidants
- Metal storage proteins
- enzymes that act as free radical scavenging systems
Describe ATP depletion causing anaerobic glycolysis
glycogen is quickly depleted
lactate and inorganic phosphate produced
drops intracellular pH
what is the sentinel event for irreversible injury of a cell
damage to membranes
Types of necrosis
Coagulation
Liquefaction
Caseous
Fat
what is coagulation necrosis
most common
usually occurs after irreversible ischaemic cellular damage
denaturation of cytoplasmic proteins with preservation of framework of the coagulated cell
What is liquefaction necrosis
when autolysis and heterolysis prevail over protein denaturation
necrotic area that is soft and filled with fluid
What is caseous necrosis
soft friable cheesy material
amorphous eosinophilic material with cell debris
eg tuberculous lesion
what is fat necrosis
necrosis in adipose tissue
chalky white area - fat saponification
morphological features of apoptosis
Cell shrinkage
Chromatin condensation and fragmentation
Cellular blebbing and fragmentation of apoptopic bodies
Phagocytosis
Lack of inflammation
Biochemical features of apoptosis
Protein cleavage by caspases
Protein cross linking by transglutaminase
Cleavage of DNA
Plasma membrane alterations - recognition of dead cells by macrophages
what is the extrinsic pathway in Apoptosis
Death receptor initiated
TNF and Fas receptors on cell surface contain a death domain that when activated leads to activation of intracellular caspases
What is the intrinsic pathway in Apoptosis
Mitochondrial pathway
Loss of survival signals or cell stress causes change in protein expression on mitochondrial surface and increased permeability to cytochrome C
Define dysplasia
loss in the uniformity of individual cells and in their architectural orientations
Exhibit considerable pleomorphism
what type of wound healing are surgical wounds
primary intention
what is the wound strength when sutures are removed at 1 week
10%
order of WBC extravasation
Rolling along the vessel wall
Activation
Adhesion to endothelium
Transmigration
what inflammatory markers are responsible for fever
Interleukin 1
TNF
Prostoglandin
What is the most common mechanism of vascular leakage in acute inflammatory response
endothelial cell contraction
What is dystrophic calcification
Occurs in nonviable or dying tissue in all area of necrosis
formed by crystallin calcium phosphate
Often causes organ dysfunction
Reversible cell injury features
cell swelling
fatty change
plasma membrane blebbing
loss of microvilli
mitochondrial swelling
dilation of the ER
eosinophilia
clumping of chromatin
in wound healing when is neovascularisation maximal
day 5
in wound healing when does neutrophil infiltration occur
24 hours
what happens by day 3 in wound healing
neutrophils have been largely replaced by macrophages
granulation tissue progressively invades the incision space
what is a normal and what is an anaplastic nuclear to cytoplasmic ratio
normal 1:4 or 1:6
anaplasie 1:1
loss of which of the following extracellular matrix components has most likely occurred in osteoarthritis?
Hyaluronan
loss of articular hyaline cartilage
what is the first thing to occur in inflammation
vasoconstriction lasting only seconds
chronic inflammation is characterised by these sets of reactions
- Infiltration with mononuclear cells including macrophages, lymphocytes, plasma cells
- Tissue destruction, largely induced by inflammatory cells
- Repair involving new vessel proliferation and fibrosis
In acute inflammation what are the changes in vascular caliber and flow?
Transient vasoconstriction
Vasodilation
locally increased blood flow
Microvasculature becomes more permeable
Protein rich fluid moves into the extravascular tissues, causing RBC more concentrated
slowing of circulation, stasis
Leukocytes accumulate, margination.
what contribute to wound contraction
Myofibroblasts
Epithelial closure in healing by primary intention occurs when?
24 to 48 hours
What cells are first involved in healing
neutrophils
What is the triple response of Lewis
Redness, Flair, Wheal
Redness - direct effect of injury causing capillary dilation
Flair - arterial dilation by substance P, CGRP
Wheal - oedema
what mediators control vasodilation in inflammation
Prostoglandins
NO
Histamine
what mediators control increased vascular permeability in inflammation
Histamine and serotonin
C3a and C5a
Bradykinens
Eukotreins C D
PAF
Substance P
what mediators control chemotaxis, leukocyte recruitment and activation
NF I
Chemokines
C3a C5a
Eukotriene B
What mediators control fever in inflammation
IL1
TNF
Prostaglandins
what mediators control pain in inflammation
Prostaglandins
Bradykinin
what mediators control tissue damage in inflammation
lysosomal enzymes of leukocytes
reactive oxygen species
NO
what is pain mediated by during the inflammatory process?
Bradykinin
3 mechanisms that inactivate free radical reactions
Glutathione (GSH) peroxidases
Catalase
Endogenous or exogenous antioxidants (vitamine E, A, C)
What do RAS proteins do
transduce signals from growth factor receptors that have intrinsic tyrosine kinase activity
Transducing the mitogenic signal from the epidermal cell membranes to the nucleus
What is dystrophic calcification
happens in any type of necrosis
inevitable in atheromas
formed by crystalline calcium phosphate mineral
what are macrophages derived from
monocytes
In injury what are the two phases of calcification?
- Initiation
extracellular, membrane bound vesicles
intracellular occurs in mitochondria - Propagation
In acute inflammation what is exudate
Inflammatory extravascular fluid, high protein concentration, cellular debris, sepcific gravity >1.020
In acute inflammation what is transudate
Fluid with low protein content, specific gravity <1.012
Define pus
Inflammatory exudate rich in leukocytes (neutrophils), debris of dead cells and microbes
3 steps of phagocytosis
- recognition and attachment
- engulfment
extension of cytoplasm (pseudopods) flow around the particle - killing and degradation
morphologic patterns in serous inflammation
moderate inflammation with few pro-inflammatory mediators
limited lymphocyte activation
accumulation of fluid
eg blister
morphologic patterns in fibrinous inflammation
vascular permeability allowing fibrinogen in
scarring due to conversion of fibrinogen to fibrin, called organisation
morphology of suppurative inflammation
build up of leukocytes and macrophages leading to liquefactive necrosis, build up of puss
eg abscess
morphologic patterns in ulcers
acute inflammation with sloughing caused due to location, fibrous changes at base and edge
In cell injury what are the effects of histamine
Dilation of arterioles
Increased permeability of venules
acts on microcirculation mainly via binding to H1 receptor on endothelial cells
in cell injury what is Serotonin (5HT)
actions similar to histamine
present in platelets and enterochromaffin cells
In acute inflammation what is the Classical Complement pathway
Triggered by C1 to antibody combined with antigen
activates C3 to C3 a and C3 b
1. C3a and C5a causes inflammation
2. C3b causes phagocytosis
3. Formation of Membrane Attack Complex from C5b to C9
In acute inflammation what is the Alternative Complement pathway
triggered by microbial surface molecules
then the complement pathway from C3 to C9
In acute inflammation what is the Lectin Complement pathway
Plasma mannose-bidning lectin binds to carbohydrates on microbes which activates C1 and so on to C3 C5 and MAC
in acute inflammation what is the role of kinins
Converts plasma proteins called kininogens by kallikreins to vasoactive peptides kinins
results in the release of bradykinin that causes;
- increased vascular permeability
- contraction of smooth muscle
- dilation of blood vessels
- pain
In acute inflammation what are the actions of Platelet Activating Factor (PAF)
stimulates platelets
vasoconstriction
bronchoconstriction
increased leukocyte adhesion to endothelium, chemotaxis, degranulation, oxidative burst
what do macrophages secrete associated with tissue injury
Proteases
Chemotactic factors
Arachidonic acid metabolites
Reactive oxygen species
NO
Coagulation factors
Complement components
what products do macrophages produce associated with fibrosis
growth factors
Cytokines IL - 1 TNF
PAF
in inflammation what is the main cell type after 48 hours
Macrophages
What are the 3 major steps in Fibrosis
Angiogenesis
Scar formation
Scar remodelling
with regards the healing by first intention what happens initially
a clot
with regards to healing by first intention what happens at 3-24 hours
neutrophils infiltrate the clot
epithelial closure by 24-48hr
in healing by first intention what happens at Day 3
neutrophils have been replaced by macrophages
granulation tissue
in healing by first intention what happens at day 5
Incision space is filled with granulation tissue
maximal neovascularisation
appearance of collagen fibrils
maximal epithelial proliferation
in healing by first intention what happens at week 2
proliferation of fibroblasts
continued collagen accumulation
production of a scar
collagen deposited early is type III, replaced by adult type I
what % of total body weight is Extracellular fluid
20%
in a bag of 0.9% NaCl how much does it contain of;
NaCl in grams
mmols /L of Na
pH range
osmolality
9 grams
150mmomls/L
4-7.0
300mOsm
which has highest Mg, phosphate and potassium concentraion ECF or ICF
ICF
The ratio of HCO3- ions to carbonic acid at a pH of 7.1 is?
10
Hydrogen iron concentrations with these pH
4.5
7.0
7.7
8.0
4.5=0.03
7.0=0.0001
7.7=0.00002
8.0=0.00001
what does Calmodulin do to smooth muscle
causes smooth muscle contraction
it binds to Ca activating myosin light chain kinases
this with ATP activates myosin to bind to Actin for contraction
what is bradykinin
a potent endothelium dependent vasodilator
contraction of visceral muscle ( non vascular smooth muscle)
increases vascular permeability
involved in mechanism of pain
what are the 3 fibre typres
A B C
what are the A nerve fibre types
alpha = somatic motor, proprioception
beta = touch, pressure
gamma - motor to muscle spindles
delta = pain, temperature, touch
what are the B nerve fibre types
preganglionic autonomic
what are the C nerve fibre typres
post ganglionic sympathetic
dorsal root pain temperature
in smooth muscle contraction what is the
I band
H zone
A band
I band = only actin, decreases
H zone = only myosin, decreases
A band = length of myosin, unchanged
What occurs after stretching intestinal smooth muscle?
it depolarises
contracts
increase in tone
increasing extracellular potassium ion concentration will do what to the resting membrane potential
decrease it
what is the main inhibitory neurotransmitter of the spinal cord
Glycine
what are the principle hypothalamic regulatory mechanisms
Temperature
Hunger
thirst
sexual behaviour
neuroendocrine control
defensive reactions
body rhythms
what is the kappa receptor is responsible for
analgesia
diuresis
sedation
dysphoria
miosis
slow GIT
what is the Mu receptor responsible for
analgesia
respiratory depression
constipation
euphoria
sedation
miosis
modulation of hormone and neurotransmitter release
what is the Delta receptor responsible for
analgesia
modulation of hormone and neurotransmitter release
what gas penetrates CSF the fastest
CO2
what is the major excitatory transmitter in the spinal cord
Glutamate
what is transmitted through the lateral spinothalamic tract
pain and temperature
what is transmitted through the anterior spinothalamic tract
crude touch
pressure
what do the dorsal columns transmit
fine touch, two point discrimination
proprioception
vibration
how is the sensation of cold transmitted
by lateral spinothalamic tracts
is a crossed sesorimodality
mediated by type A delta fibres
relayed by the thymus
Anterolateral dissection of the spinal cord is associated with
Ipsilateral hyperreflexia
as it causes damage to lateral corticospinal tract which decussates at the pyramids
loss of control of motor function
what does MOA-A break down
Serotonin
melatonin
Noradrenaline
Adrenaline
dopamine, tyramine, tryptamine
what does MOA-B break down
Phenethylamine
benzylamine
dopamine, tyramine, tryptamine
in the formation of adrenaline what is the sequence
Tyrosine -> Dopa -> Dopamine ->noradrenaline -> adrenaline
in formation of adrenaline ho is Dopa formed
from tyrosine hydroxylase
Tyrosine -> Dopamine
what metabolises noradrenaline and adrenaline to inactive products
COMT
MOA
regarding carbohydrate homeostasis in exercise what happens
initially muscle utilizes glycogen stores
also muscle increase uptake of glucose
Plasma glucose initially rises with increased hepatic glycogenolysis
Insulin falls
The majority of heat lost by the body at 21 degrees is by
radiation
what does ATP consist of
3 phosphate groups
an adenine ring
ribose sugar
what do thyroid hormones do to LDL receptors
increase them
resulting in hepatic removal of cholesterol
what does PTH do to PO4
decreases it
what does PTH act on
directly on bone to increase resorption and mobilize Ca
what does phenytoin, noradrenaline and somastatin do to insulin
inhibit insulin secretion
what cells produce Glucagon
alpha cells of the pancreas
what does Glucagon do
stimulate gluconeogenesis to produce glucose
half life 5-10 mins
What is T4 synthesised from and held in
synthesised from tyrosine
held in thyroglobulin
Where are T3 and T4 metabolized
liver and kidneys
A deficiency of parathyroid hormone (PTH) is likely to lead to
rise in phosphate and a decrease in plasma Ca
neuromuscular hyperexcitability
what happens to glycogen and glucose with Glucocorticoids
increase glycogen synthetase
decrease peripheral glucose utilisation
plasma glucose level rises
where is B12 absorbed
ileum
what can increase iron absorption
vitamin C
where does protein digestion begin
stomach
what are the nutritional essential amino acids
Threonine
Valine
Leucine
Isoleucine
Methionine
Phenylaanine
Lysine
The majority of water ingested is re-absorbed where
Jejunum
what do parietal cells secrete
Intrinsic factor
what do chief cells secrete
pepsinogen and rennin
what do eosiophils phagocytose
parasites
what is the half life of neutrophils
6 hours
describe the protein in lymph
it has different protein content in different areas
what do prostoglandins to medullary blood flow and cortical blood flow
decrease medullary blood flow
increase cortical blood flow
what thins contribute to venous blood flow
the pumping of the heart
skeletal muscle contraction
intrathoracic pressure variations
Where in the kidney is the tubular fluid isotonic with the renal interstitium?
PCT
(water moves passively out of the tubule along the osmotic gradients set up by the active transport of solutes. This maintains isotonicity)
what is the anion gap calculation
Na - (Cl + HCO3)
what type of anion gap is caused by diarrhoea which causes metabolic acidosis
normal anion gap
what type of anion gap metbolic acidoses does uraemia and rhabdo cause
raised
Which of the following H+ concentration is compatible with life?
0.00000004 mol/l
where is carbonic anhydrase found
RBC
gastric acid secreting cells
renal tubular cells
NOT in plasma cells
In chronic acidosis, the major adaptive buffering system in the urine is
Ammonium
what is hyperopia
Eye too short for refractive power of cornea and lens-
Light focused behind retina
what is myopia
Eye too long for refractive power of cornea and lens-
light focused in front of retina
what is astigmatism
Abnormal curvature of cornea-
different refractive power at different axes
what is presbyopia
Age related impaired accommodation.
(Focusing on near objects),
primarily due to decrease lens elasticity. Often necessitates “reading glasses.”
A deep sea commercial diver presents to the ED after suffering a seizure. He has no known seizure activity. What gas is primarily responsible?
Oxygen
what substances does the saliva contain
Na, K, Ca, Mg, Cl, HCO3, PO4, iodine
Mucins (to lubricate food)
IgA, hydrogen peroxide
Epidermal growth factor
alpha-amylase, lingual lipase, kallikrein, antimicrobial enzymes (lysozyme, lactoperoxidase, lactoferrin)
Opiophin: a pain killing substance
Haptocorrin: protein that’s binds B12 to protect it against degradation in the stomach before it binds to intrinsic factor
stimulators of endothelin-1
Angiotensin II
Catecholamines
GF
hypoxia
insulin
oxidised LDL, HDL
shear stress
thrombin
Inhibitors of endothelin-1
NO
ANP
PGE2
prostacyclin
Where are steroids synthesised in steroid secreting cells?
Smooth endoplasmic reticulum
what is the main exitatory transmitter in the brain and spinal cord
Glutamate
Inhibitors of glucagon
Somatostatin
Secretin
FFA
Ketones
Insulin
Phenytoin
Alpha-adrenergic stimulators
GABA
stimulation of glucagon
Amino acids
CCK, gastrin
Cortisol, exercise, infections and other stressors
B adrenergic stimulators
Theophylline and acetylcholine
stimulators of gastric acid secretion
Gastrin
ACH
histamine
Inhibitors of gastric acid secretion
VIP
Prostaglandins
Which hormone stimulates an increase in the volume of pancreatic juice but not the enzyme content?
Secretin
Which hormones stimulate an increase in the enzyme rich pancreatic juice?
CCK
ACH
Vagus nerve
Which organ has the greatest blood flow through it in ml/min?
Liver
Which organ has the highest percentage of blood flow per 100g?
Kidney
what are type II muscle fibres
Fast glycolytic white
used for sprinting
Describe type IIa and IIb muscle fibres
IIa - Fast, Oxidative, Glycolytic (FOG) –> Red muscle –> Moderate oxidative capacity –> Fast, fatigue resistant (FR)
IIb - Fast, Glycolytic (FG) –> White muscle –> Low oxidative capacity –> Fast, fatigable (FF)
Type II muscle fibre characteristics
Myosin isoenzyme ATPase rate= fast
Calcium pumping capacity of sarcoplasmic reticulum=High
Diameter= large
Glycolytic capacity= high
Oxidative capacity= Low
is endothelin-1 a vasoconstrictor of vasodilator
vasoconstrictor
what happens to level of endothelin-1 in CCF or after mI
increased
where is endothelin-1 found
endothelial cells
brain
kidney
where is calcitonin found
parafollicular cells of the thyroid
when is Calcitonin secreted
presence of high calcium concentration
what is the role of calcitonin on calcium and phsophate
lowers circulating calcium and phosphate levels
inhibits bone resorption, increases Ca excretion in the urine
EPSP (excitatory postsynaptic potentials)
produced by depolarization of the postsynaptic cell membrane immediately under the presynaptic ending.
The excitatory transmitter opens NA or Ca channels producing an inward current.
The area of current flow is so small that it does not drain enough positive charge to depolarize the whole membrane. Instead an EPSP is created.
how do EPSPs (excitatory postsynaptic potentials) produce depolarization/ a response
Activity present in more than one synaptic knob at the same time creates spatial summation.
Repeated afferent stimuli causing new EPSPs before the old EPSPs has decayed is temporal summation.
therefore NOT all or nothing response but are proportionate in size to the strength of the afferent stimuli.
what is equal to the molar mass of a substance divided by its valence
Equivalents
what secretes secretin
S cells
located deep in the glands of the mucosa of the upper portion of the small intestine
what does secretin do
decreases gastric acid secretion
causes pylorus sphincter contraction
increased secretion of HCO3 by the duct cells of the pancreas and biliary tract
augments action of CCK producing pancreatic secretion of digestive enzymes
what triggers the secretion of secretin
protein digestion
acid bathing in the mucosa of the upper small intestine
when does ketoacidosis occur
occurs in starvation, diabetes mellitus and a high fat, low carbohydrate diet
what causes ketotic breath odour
due to the acetone ketone body
When extra blood is transfused, where is it NOT distributed?
left ventricle
where is the absorption of CSF
through arachnoid villi into veins
mainly cerebral venous sinus
Ammonia is secreted into the tubular fluid as what molecule
NH3
in Urine what happens to NH3 (ammonia) and why
it reacts with H+ to become NH4+ (ammonium)
this is to maintain the gradient of NH3 for diffusion of ammonia
called nonionic diffusion
in the collecting ducts
6 hormones secreted by the anterior pituitary gland
TSH
ACTH
LH
FSH
prolactin
growth hormone
B-lipitropin
2 hormones secreted by the posterior pituitary are
oxytocin
vasopressin
what increases 2,3 DPG
thyroid hormones
growth factor
androgens
exercise after 60mins
Which dopaminergic systems are important for the understanding of schizophrenia
Mesolimbic-mesocortical pathway
what % of total blood volume is plasma
55%
how long does it take for the total blood volume to circulate around the body at rest
one minute
In cardiac and skeletal muscle wat triggers contraction
calcium binding to troponin C
how does the body temperature fluctuate in a day
the temperature is lowest at about 06:00 and highest in the evenings
what is cAMP known as
3 5 - monophosphate
how is cAMP formed
formed from ATP by adenylyl cyclase
what nerve supplies the external sphincter
pudendal nerve
when does the first urge to defecate happen
at a rectal pressure of 18mmHg
where does protein digestion begin and by what
stomach
by pepsin
where is pepsinogen I found
only in the acid secreting regions of the stomach
what is pepsins optimal pH
1.6 - 2.3
what shifts the haemaglobin dissociation curve to the right
rise in temp
decrease in ph
increae 2,3 DPG
rise in CO2
where is aldosterone secreted
produced by the outer section (zona glomerulosa) of the adrenal cortex
what is the action of aldosterone on the kidneys
promotes sodium reabsorption
potassium secretion
what is the resting potential od a neuron
-70mV
stimuli that decrease secretion of growth hormone
REM sleep, glucose, cortisol, FFA, medroxyprogesterone, and IGF-1
what happens after a glucose load in a non diabetic person
50% is normally burned to H20 and CO2,
5% is converted to glycogen
30-40% is converted to fat in the fat deposits.
what happens after a glucose load in a diabetic person
Less than 5% is converted to fat, a decrease in the amount burnt to CO2 and H2O
no change in the amount converted to glycogen.
glucose accumulates in the blood stream and spills over into the urine.
stimulants of Corticotropin releasing hormone
Trauma via the nociceptive pathways,
emotions via the limbic system,
the drive for the circadian rhythm
Inhibition of corticotropin releasing hormone CRH
Baroreceptor exert an inhibitory (afferent) input via the nucleus of the tractus solitarius.
Which metabolite is responsible for maintaining normal parathyroid functioning?
Magnesium
what do T4 and T3 NOT increase oxygen consumption for
adult brains,
testes, uterus,
lymph nodes,
spleen,
the anterior pituitary gland
what controls thirst
Thirst is under anterior hypothalamus control via osmoreceptors.
Demyelination in the CNS affects which cells
oligodendrocytes
Demyelination of the PNS effects which cells
Schwann cells
PO2=%sats of Hb
10 %?
20 %?
40 %?
50 %?
60 % ?
90 %?
100 %?
PO2=%sats of Hb
10-13.5
20-35
40-75
50-83.5
60-89 (90)
90-96.5
100-97.5
To diagnose the syndorme of inappropriate ADH secretion (SIADH), you need the following?
Euvolaemic hyponatraemia <135mmol/L
Plasma osmolality <280mOsm/L
Urine osmolality >100mOsm/L
Urine sodium >20mmol
Urine osmolality>serum osmolality
What is the main negative intracellular charged molecule found in the intracellular fluid?
Protein
Regarding nerve fibre type and functions, which of the following nerve fibre is most susceptible to hypoxia?
Type B
Which of the cell organelles is found in the greatest number in growing cells and synthesise ribosomes?
nucleoli
Local anaesthetics work most strongly on which fibres?
Type C (unmyelinated)
C -> B ->A
In intracellular and extracellular fluids what is the Na and K ?
NA
Intracellular = 15mmol/L
Extracellular = 150mmol/L
K
Intracellular = 150mmol/L
Extracellular = 5.5mmol/L
Which substances are responsible for the increase in the formation of plasmin
Activated protein C
Protein S
what inhibits release of prolactin
dopamine, apomorphine and bromocriptine
Effects of insulin on liver
Decreased ketogenesis
Increased protein synthesis
Increased lipid synthesis
Decreased gluconeogenesis, increased glycogen synthesis, increased glycolysis
what is the oxygen carrying capacity of Hb
1.34ml/g
Haemoglobin increases the oxygen carrying capacity of blood/plasma by a factor of:
70 times
describe absorption of vitamin B12
binds to intrinsic factor and is absorbed in the terminal ileum.
what does vitamin B12 deficiency cause
megaloblastic pernicious anaemia
degeneration of posterolateral spinal cord tracts (tingling sensation)
What is the principle mechanism by which carbon monoxide exposure induces hypoxia?
Reducing the oxygen carrying capacity of Hb
What is the order of the structures conveying visual sensation?
Optic nerve,
optic chiasm,
optic tract,
lateral geniculate body,
occipital cortex
What is the approximate % of blood volume located in the venous system at rest?
50-60%
Which structure in the eye is directly responsible for accommodation?
ciliary muscle
Hydrogen ions are secreted primarily in the form of:
free form
(then buffered via NH4, H2PO4 and bicarbonate to facilitate further secretion.)
Where is most iron absorbed in the gastrointestinal tract?
duodenum
facilitated by ferric reductase
Mitochondria use what percentage of oxygen?
90%
The function of nerve fibres with the largest diameter is:
proprioception and motor
type A alpha
Where is proprioception and vibration transmitted in the spinal cord?
Dorsal column
What will be the effect of haemorrhage on the vasopressin osmotic response curve, and plasma Na?
Shifted upwards and to left, decreased plasma Na
Which hormone increases gastric acid secretion, stimulates gastric mucosa proliferation, and stimulates gastric emptying?
Gastrin
What is the major buffer in intracellular fluid?
phosphate and proteins
In the action potential of a spinal motor nerve, sodium does not reach equilibrium because of which of the following processes?
Closure of Na Channels
What makes up 20% of body weight?
ECF
At what altitude does oxygen concentration significantly drop off?
34000feet/ 10400m
You test a gentleman’s vibration sense with a 126Hz tuning fork. Where does this travel?
medial lemniscal pathway
What proportion of ATP is used in the cell for gluconeogenesis?
9%
A hypoglycaemic patient has the following blood results: Na = 120, K = 6.7. What is the likely cause?
Primary adrenal insufficiency
TRH stimulates which hormone other than TSH?
Prolactin
The main function of the colon is to
allow for the reabsorption of water, sodium, and other minerals
A patient suffers peripheral vision loss in both the right and left eyes, with macular sparing. Where is the lesion?
occipital lobe
What spinal tract is primarily responsible for motor control of voluntary movements?
lateral corticospinal tract
What percentage of an oral glucose load is typically metabolized into fat under conditions of excess caloric intake?
30-50%
What are the functions of the smooth endoplasmic reticulum?
Steroid synthesis
carbohydrate metabolism
drug metabolism
calcium regulation
lipid synthesis
gluconeogenesis
Which cell type is found predominantly in the periarteriolar sheaths in the white pulp of the spleen?
T lymphocyte
Which of the cell organelle have no phospholipid bilayer membrane?
Centriole
Regarding ribosomes;
what doe they synthesise
what are they divided into
protein, haemaglobin
two subunits - 65% RNA 35% protein
Regarding dystrophic calcification;
where does it occur
what is the serum calcium
what type of calcium deposition
what type of necrosis does it occur in
in damaged or dying tissues
normal serum calcium levels
formed by crystalline calcium phosphate
occurs in all areas of necrosis
in a cell what are the characteristics of irreversible cell injury
lysosomal rupture
disruption/defects of cellular membranes
depletion of ATP
products in macrophages that cause tissue injury and fibrosis are
arachidonic
metabolites
reactive oxygen species
reactive nitrogen
proteases
cytokines
coagulation factures
products in macrophages that cause repair
Growth Factor
Fibrogenic cytokines
angiogenic factos
remodelling collagenesis
where does metastatic calcification normally occur
gastric mucosa
kidneys
lungs systemic arteries and pulmonary veins
in the complement system what are the main things C5a does
chemotatic for neutrophils
activates the lipoxygenase pathway of arachidonic acid AA metabolism
increases vascular permeability
in the complement system what is the main function of C3b
when fixed to bacterial cell walls act as opsonins and promote phagocytosis by neutrophils and macrophages
where are mast cells derived from
bone marrow
what provides the energy for mast cell degranulation
Adenosine triphosphate (ATP)
factors released by macrophages
toxic oxygen metabolites
proteases
neutrophil chemotatic factors
coagulation factors
arachidonic AA metabolites
NO
GF
angiogenesis and remodelling collagenases
TNF
IL-1 IL6 IL12
Chemokines
what are the steps of phagocytosis
- recognition and attachment
- engulfment
- degradation
what molecules are involved in migration of leukocytes to site of injury
PECAM 1
(platelet endothelial cell adhesion molecule)
ICAM
(intercellular adhesion molecule)
CD31
where is C3b derived from and where is it formed
derived from the liver
formed in plasma
where is histamine derived from
mast cells
basophils
platelets
where is the kinin system activated
plasma
where is nitric oxide produced in inflammation
macrophages
characteristics of non inflammatory oedema/transudate
low protein content <2g/dl
specific gravity <1.012
serum cholesterol <45mg/dl
caused by increased hydrostatic pressure and
decreased plasma colloid pressure
elevated ANP
right atrial pressure is high
Regarding increased vascular permeability due to endothelial contraction, where is it most common
in venules
Pathophysiologic categories of oedema
Increased hydrostatic pressure
Reduced plasma oncotic pressure
Lypmhatic obstruction
Sodiu retention
Inflammation
with amniotic fluid embolism what is;
the rate
the mortality %
risk factors
1:40000
80%
Tumultuous labour, multigravids
in the coagulation cascade describe the common pathway
Factor X has been activated
FXa activates FII ( prothrombin) to FIIa (thrombin)
FIIa activates FI (Fibrinogen) to FIa (fibrin)
then leading to stable fibrin clot
In Haemophilia A;
what is the factor deficiency
what % cause disease
what is prolonged
FVIII
<1% is severe, 2-5% is moderate, 6-50% is mild
prolonged PTT
what is passive hyperaemia and what can cause it
congestion or stasis
caused by;
portal hypertension
congesitve cardiac failure
hepatic obstruction
definition of shock
cellular hypoxia resulting from impaired tissue perfusion
Regarding fat embolism;
when does it occur
what is fat embolism syndrome
fatality %
symptoms/findings
occurs in 90% of individuals with skeletal injuries, symptoms develop 1-3 days after injury
Fat embolism syndrome is when patient become symptomatic (<10%) - pulmonary insufficiency, neurological symptoms, anaemia, thrombocytopenaoa
10% fatal
can cause diffuse petichial rash 20-50% of cases
features of post mortem clot
gelatinous due to lack of fibrin
dark red portion of red cells
yellow chicken fat upper portion
usually not attached to underlying wall
in blood vessels what are lines of Zahn
represent pale platelet and fibrin deposits alternating with darker red cell rich layers
signify a thrombus has formed in flowing blood
does pulmonary oedema occur because of right or left sided heart failure
left sided heart failure
AIDS defining infections include
Protozoal and helminthic - pneumocytosis, toxoplasmosis, cryptosporidiosis.
Fungal - candida, cryptococcus, disseminated histoplasmosis, coccidioidomycosis.
Bacterial - mycobacterium, disseminated salmonella infections.
Viral - CMV, HSV, VZV.
AIDS defining neoplasms include;
Kaposi sarcoma,
beta cell non-Hodgkin lymphoma,
primary lymphoma of the brain
invasive cancer of the uterine cervix
with regards to hyperacute graft rejection;
when does it occur
how is it decreased
how is it mediated
within minutes to hours
decreased with cross matching
reaction is Ag and Ab (Immunoglobulin deposition ) mediated
these complexes are in the vessel wall, causing endothelial injury and fibrin-platelet thrombi
with regards to the Rhesus blood group;
what % of Caucasians are Rh +ve
are there spontaneous agglutinins
when do transfusion reactions occur
85%
spontaneous agglutinins never occur
first transfusion of Rh+ blood will create anti D titres, this will cause a transfusion reaction any time in the future if transfused again
regarding T lymphocytes;
where do they develop
what % of blood lymphocytes
what forms the TCR complex
what type of hypersensitivity
thymus
60-70%
T cell receptor plus CD3 form TCR complex
Type IV hypersensitivity
type 1 hypersensitivity primary mast cell mediators
Heparin
Adenosine
Histamine
Eosinophil chemotatic factor
neutrophil chemotatic factor
tryptase, chymase, acid hydrolase
type 1 hypersensitivity secondary mast cell mediators
Platelet aggreating factor
prostaglandin D2
leukotrienes
cytokines - NF IL 1 3 4 5 6
what is type I hypersensitivity and examples
Immediate IgE
anaphylaxis, allergies, asthma
what is type II hypersensitivity and examples
antibody dependent
autoimmune haemolytic anaemia, erythroblastosis fotalis, rheumatic fever, goodpastures, graves disease
what is type III hypersensitivity and examples
Immune complex
SLE, glomerulonephritis, Arthus reaction, serum sickness
what is type IV hypersensitivity and examples
Delayed
MS, TB, contact dermatitis, T1DM, RA, IBD, graft vs host disease
OCP is protective against
endometrial and ovarian cancer
most common type of thyroid cancer
Papillary 75-80%
Acanthosis nigricans is associated with what cancer
Gastric, lung, uterine
With secondary syphilis;
are lesions painful?
is palm and sole sparing?
when does it occur ?
are lesions infectious?
painless lesions
occurs on palms and soles
occurs 2-10 weeks post primary
infectious as they contain spirochetes
how do bacterial endotoxins play a role in septic shock, ARDS and DIC?
through excessive levels of cytokines
TNF and IL-1
In serous pericarditis how is it produced
Produced by non infectious inflammatory diseases
rheumatic fever, SLE, scleroderma
tumours
uraemia
in myelofibrosis what type of anaemia occurs
normochromic normocytic pancytopenic anaemia
accompanied by leukoerythroblsastosis
describe the pathology of myelofibrosis
Myelofibrotic obliteration of the marrow space leads to extensive extramedullary haematopoeisis, principally in the spleen.
in bone marrow, more megakaryoctes form, increasing platelet production and cytokines
the cytokines increase fibrosis in the bone marrow
therefore the haematopoitic cells from the bone marrow deposit elsewhere = extramedullary haematopoeisis
How does unconjugated bilirubin travel in the body
is insoluble
tightly bound to albumin
cannot be excreted
deposited in tissues
in babies can deposit in the brain and cause kernicterus
in cirrhosis what is the major source of excess collagen
perisinusoidal hepatic stellate cells (Ito cells)
In pancreatitis what does trypsin do
activates prekallikrein to its active form
main causes of pancreatitis
80% of cases are associated with 2 conditions; biliary tract disease and alcoholism.
Gallstones are present in 35-60% of cases of pancreatitis,
and about 5% of patients with gallstones develop pancreatitis
Is diabetes mellitus in acute or chronic pancreatitis
chronic pancreatitis
what causes post infectious glomerulonephritis
group A beta haemolytic streptococcus eg impetigo
Which of the following is correct in relation to nephrotic syndrome?
A. Hypertension
B. There is alteration to serum lipid levels
C. Albumin is lost, other globulins are unaffected
D. Decreased interstitial fluid volume
B There is alteration to serum lipid levels
with ATN (acute tubular necorisis) when does hypokalaemia happen
in the recovery phase
which type of ATN has better recovery
non-oliguric
which part of the nephron are most vulnerable in ATN
straight portion of the proximal tubule and the ascending thick limb
what % of ATN patients have anuria
50%
3 stages of ATN
initiating stage,
maintenance stage (decreased urine output)
a recovery stage
what happens to urine in hepatorenal syndrome
kidneys maintain ability to concentrate urine
oliguria with hyperosmolar urine
no proteins
low Na
what type of kidney stones does leukaemia cause
uric stones
due to high cell turnover and resulting hyperuricaemia
what are struvite stones made of
magnesium-ammonium-phosphate
types and % of renal stones
Calcium oxalate stones 70%
Struvite stones 15%
Uric acid stones 5-10%
Cysteine stones 1%
Posterior pituitary releases?
Oxytocin
Antidiuretic Hormone
Anterior pituitary releases
TSH
Adrenocorticotrophic hormone (ACTH)
FSH
LH
GH
Prolactine
Melanocyte stimulating hormone (MSH)
describe Rickets
disturbance of bone mineralisation
defect in matrix mineralization, most often due to vitamin D deficiency or vitamin metabolism.
describe Pagets Disease
Paget’s Disease: osteoclastic bone activity and hectic bone formation.
what causes osteomalacia
It is caused by a 1,25(OH)2DH3-calciferol deficiency
PTH is increases
Which cytokine produced by macrophages is the most important stimulator of fibroblasts?
TGF - transforming growth factor
Which hypersensitivity reaction is poststreptococcal glomerulonephritis?
Type III
A 6yr female presents to the ED with gingivostomatitis. Which virus is the likely cause?
HSV
An intravenous drug user presents to the emergency department with suspected osteomyelitis of the ankle.
Which organism is frequently isolated in this type of patient?
E coli
Pseudomans
Klebsiella
A patient presents to the ED. This is his 5th presentation since suffering from a bout of pneumonia 3yrs ago. His main clinical findings are cough, purulent sputa and fever. What is the most likely diagnosis?
Bronchiectasis
a disorder in which there is destruction of smooth muscle and elastic tissue by chronic necrotizing infections leading to permanent dilation of bronchi and bronchioles.
Extrinsic and common coag pathway assesses what in coagulation blood test
Prothrombin time
Intrinsic pathway assesses what in the coagulation blood test
PTT
partial thromboplastin time
What is the route of transmission of Hepatitis E?
Foecal oral route
The incubation period of Hepatitis B is
14-182 days
characteristic of the rash of measles?
Maculopapular eruption starting on upper trunk and spreading downward.
Alkalinisation of urine may precipitate which of the following renal calculi?
Struvite stones
In which part of the CNS does polio not affect?
Dorsal root ganglion
What is agammaglobulinemia
X-linked agammaglobulinemia
characterised by the failure of B cell precursors to develop into mature B cells.
appear only after 6 months of age
Recurrent bacterial infections of the respiratory tract are the most common and allude to the underlying immune deficiency.
Which is the most most common infection to complicate burns?
pseudomonas aeruginosa
the two main aetiologies of atraumatic intracerebral haemorrhage
HTN
cerebral amyloid angiopathy
what is the cellular origin of retinoblastoma
neuronal cell
complications/progression of EBV in immunodeficiency
development of EBV positive tumours (which are usually but not always derived form B cells)
B cell lymphoma, nasopharyngeal Ca, Hodgkin and non-Hodgkin lymphomas and Burkitt lymphoma.
Blood film in myelofibrosis
leukoerythroblastic anaemia
what is the bilirubin in haemolytic anaemia
uncomplicated
Which cancer is associated with Cadmium?
Prostate
Cadmium is used in batteries and in metal platings and coatings
cancer markers and their tumours
Ca125
Ca 19-9
Ca 15-3
AFP
HCG
Ca 125= ovarian cancer,
Ca 19-9= colon cancer and pancreatic cancer
Ca 15-3= breast cancer.
AFP= liver cancer, nonseminomatous germ cell tumour of testis.
HCG= trophoblastic tumours and nonseminomatous testicular tumours.
where is the most common site of infection of osteomyelitis in children
metaphysis
a complication of Heparin
Heparin induced prothrombotic state
Heparin induces antibodies against platelets and endothelium (HIT). Heparin induces a thrombocytopenia (HIT).
what happens to platelets and PTT in Immune thrombocytopaenic purpura
large platelets
normal PTT
Which is the most common inherited bleeding disorder in humans?
Von Willebrand disease
type of paralysis of C. botulinum
Flaccid paralysis
type of paralysis in C tetani
Spastic paralysis
what happens in Subfalcine (cingulate) herniation:
when unilateral or asymmetric expansion of a cerebral hemisphere displaces the cingulate gyrus under the falx cerebri.
This may lead to compression of the anterior cerebral artery
what happens in Transtentorial (uncinate) herniation
occurs when the medial aspect of the temporal lobe is compressed against the free margin of the tentorium. The third cranial nerve can be compressed, resulting in pupillary dilation and impairment of ocular movements on the side of the lesion. The posterior cerebral artery may also be compressed resulting in ischaemia to the primary visual cortex.
what happens in Tonsillar herniation
displacement of the cerebellar tonsils through the foramen magnum.
The type of herniation is life threatening because it compresses and compromises vital respiratory and cardiac centres in the medulla oblongata
Which is the correct sequence of first to last laboratory abnormality seen with disseminated intravascular coagulation (DIC)?
Thrombocytopenia, elevated PT, hypofibrinogenemia
which hepatitis infection does not cause chronic liver disease
hepatitis A
what is the main disease process in OA
Chondrocyte injury
Chrondrocytes play a role in cartilage destruction
Which of the chemical mediators of inflammation are produced form arachidonic acid and generates a febrile response?
Prostoglandin
Which vitamin deficiency causes the 3 Ds?
Diarrhoa, dermatitis, dementia
Niacin
Gangrene of the great toe is associated with what type of necrosis?
Coagulative
Which of the following viruses is more commonly associated with intussusception?
Rotavirus
Apart from fibrinogen, which clotting factors does Prothrombin time test for?
II, V, VII, X
What volume ascites accumulates before becoming clinically detectable?
500mls
Which metabolite accumulates in stroke propagating cellular damage?
Glutamate
Cholera infection has the greatest impact on the GI tract
Small bowel
50-year-old woman is referred to the ED with a critically elevated Calcium level. She is asymptomatic. What is the most likely cause of her clinical picture?
solitary parathyroid adenoma
what is sick euthyroid syndrome and what would the tfts be
a biochemical pattern of decreased circulating T3 levels
normal TSH
normal T4
What are the typical pathological changes seen in bronchiectasis?
Inflammation and nerosis
What is the mechanism of edema in pleural effusion secondary to pneumonia?
leukocyte mediated inflammation
Rupture of esophageal varices has a mortality of approximately:
20%
Anti-D is sometimes given in pregnancy to prevent which type of hypersensitivity reaction?
type II
The classical complement pathway is activated by:
antigen antibody complex
Which of the following is a late change seen in an acute asthma attack?
epithelial cell damage
Which type of hypersensitivity reaction underlies the pathological changes seen in post-streptococcal glomerulonephritis?
type III
what is the first pathological change seen in primary angle closure of glaucoma
Transient iris apposition to lens
What is the most important independent risk factor in the development of atherosclerosis?
genetics
A 55-year-old man is found to have an incidental 5.5cm AAA. What is the risk of rupture per year?
5-15%
Gallstones are most commonly made up of which substance?
cholesterol
What causes acalculous cholecystitis?
ischaemia
usually in the context of septic shock or multiorgan failure.
Which morphological feature of pancreatitis has the worst prognosis?
interstitial haemorrhage
does propanolol have Na blocking activity
yes
it can cause widening of QRS and may lead to VF arrest in overdose
the CAST ONE trial highlighted adverse effects of what drug
flecainide
which is more potent frusemide or triamterene
frusemide
mechanism of action of mannitol
primarily increases urine volume
It inhibits H2O absorption in proximal tubule, loop of henle, and collecting tubule
what can delay wound healing
Glucocorticoid excess
What occurs at the same time as epithelial cell proliferation in wound healing by first intention?
Formation of granulation tissue
A concerned mother brings her 2 week old daughter to the emergency department due to yellow skin. She is otherwise well. Blood tests reveal an unconjugated hyperbilirubinaemia. What is the likely cause?
impaired conjugation
Question 368
Opthalmoplegia and neurological dysfunction in an alcoholic is most likely to response to supplementation with which vitamin?
B1
A somatotrope adenoma of the pituitary gland is likely to cause excess of?
Growth hormone
Macrophages are primarily responsible for the formation of which growth factor which promotes fibroblast migration and proliferation?
TGF
In healing by first intention, when is neovascularisation at its peak?
Day 5
An elderly man presents with subacute infective endocarditis, what is the likely cause?
strep viridans
Mantoux skin testing demonstrates what sort of hypersensitivity reaction?
Type IV cell mediated hypersensitivity
Lung abscesses are commonly associated with which pathogen?
strep pneumococcus
Which tissue is most damaged with radiation dose of 1-2Sv?
Lymphoid
Which tissue is most susceptible to radiation-induced cancer?
Lymphoid
Which of the following conditions is most likely to be associated with a prehepatic portal hypertension?
massive splenomegaly
A male presents with a pulsatile mass in his abdomen. Which of the following conditions MOST predisposes to this?
Athersclerosis
(atheroscleorsis in AAA, HTN in ascending aneurysms)
What is the most common bacterial trigger of COPD
h.influenzae
What is the most common cause of acute hepatic failure in the developed world?
Acetaminophen overdose
A young non-smoking woman presents with a 3 month history of cough with occasional blood-stained sputum. Her older brothers are married but without children. What is the most likely diagnosis?
primary ciliary dyskinesia
