Q1

List some ways in which substances are transported across cell membranes.

  • Exocytosis
  • Movement across ion channels
  • Endocytosis
  • Active transport
  • Secondary active transport

Pass Criteria:

  • 3 out of 5 to pass

Describe the sodium potassium pump.

  • Energy dependent (ATP to ADP)
  • 3 Na+ ions going out in ex-change for 2 K+ going into cells via a carrier protein
  • Give an example of secondary active transport

Pass criteria:

  • Co-transport eg: glucose with sodium, sodium with amino acids
  • Counter-transport system: eg. Sodium counter-transport with calcium and hydrogen ions

 


Q2

What factors are responsible for heat production and heat loss?

  • Heat Production
    • Basic metabolic process
    • Specific dynamic action of food
    • Muscular activity
  • Heat is lost by
    • Radiation and conduction
    • Vaporisation of sweat
    • Respiration
    • Urination and defaecation

Pass criteria:

  • 2 of each

Describe the body’s adaptive response to a cold environment.

  • Mechanisms activated by cold
    • Shivering
    • Hunger
    • Increased Voluntary activity
    • Increased Secretion of adrenaline/nor adrenaline
    • Decreased Heat loss
    • Cutaneous vaso-constriction
    • Curling up
    • Horripilatian (goose bumps)
    • (Controlled from posterior hypothalamus)

Pass criteria:

  • 3 to pass

 


Q3

What hormones are involved in serum calcium regulation?

  • PTH
  • Calcitonin
  • 1,25 DHCC

Pass criteria:

  • 2 out of 3

Outline the effects of PTH (Parathyroid Hormone).

  • Increased Parathyroid hormone secretion
  • A Kidneys –
    • Increased Calcium reabsorption
    • Increased 1,25- (OH)2D formation
    • Decreased Urinary excretion of  Calcium
    • Increased Plasma 1,25-  leads to (OH)2D  levels cause –
  • B Intestine – Increased Calcium absorption
  • Bone – Increased Resorption, Increased Release of Ca 2+ into plasma

 


Q4

Describe the structure and function of the sodium potassium ATPase pump.

  • Antiport: catalyses hydrolysis of ATP to ADP to move 3 Na out cell in exchange for 2 K in.
    • Maintains electrochemical gradient ECF (Electrogenic pump 3+ out / 2+ in = net 1+ out) and is large part of basal energy consumption  – 33% energy use by cells (70% neurons)
    • Coupled to transport other substances (secondary active transport) e.g.glucose in SI mucosa
  • alpha and ß subunits which pass through cell membrane
    • Both heterogeneous
    • alpha subunit intracellular binding sites for Na & ATP
    • alpha subunit extracellular binding sites for K & ouabain
    • ß subunit has no binding sites Na / K
    • Variable distribution of alpha 1 + 2 and ß 1+2  subunits
  • When Na binds to alpha subunit, ATP also binds. ATP is converted to ADP causing change in protein configuration extruding Na out of cell.
    • K then binds extracellularly dephosphorylating alpha subunit which returns to original configuration releasing K into cytoplasm

Pass Criteria:

  • 3 out of 5

 


Q5

How is water distributed through the body compartments?
Prompt: How much water is in the intracellular space?

  • TBW is 60% of body weight
  • ICF 2/3 of TBW
  • ECF 1/3 of TBW
  • Interstitial ¾ of ECF
  • Plasma ¼ of ECF

 

other 1

How do age and gender affect total body water?

  • Decreases with age
  • Higher in males

 


Q6

Discuss the hormonal control of calcium metabolism.
Prompt: What are the three hormones involved?

  • 1, 25 DHC, inc uptake (gut and renal)
  • PTH, inc reabsorption from bone
  • Calcitonin, decreased reabsorption from bone

Pass Criteria:

  • Reduces splanchnic blood flow

What are the secondary hormones involved?

  • GH, inc gut reabsorption
  • Glucocorticoids, inc bone reabsorption
  • Oestrogens, inhibit osteoclasts

How does high calcium affect the mechanism you just discussed?

  • Decreased 1,25 DHC
  • Decreased PTH

 


Q7

How is iron absorbed from the gastro-intestinal tract?

  • As heme iron (bound) or free iron
  • Heme iron absorption independent of pH
  • More Fe2+ (soluble form) with gastric acid
  • Affected by other gut contents
  • In small bowel
  • Binds to apoferritin
  • Transported to portal circulation
  • Feedback alters rate of absorption

How is iron transported?

  • Free Fe2+ bound to transferrin
  • To liver then bone marrow

Physiologically, how is iron lost from the body?

  • Gut cells
  • Menstruation

 


Q8

What are the actions of vitamin D?

  • Increased absorption of calcium from the intestine by induction of calbindin-D proteins.
  • Increased resorption of calcium in the kidneys.
  • Increased osteoblast activity
  • Aids calcification of bone matrix.

Pass Criteria:

  • 3 out of 4

How is the synthesis of vitamin D regulated?

  • Not closely regulated.
  • Low calcium leads to increased PTH secretion and increased vitamin D is produced.
  • High calcium inhibits PTH and the kidneys produce inactive metabolites.
  • Low phosphate increases vitamin D production (and high phosphate inhibits it).
  • Vitamin D inhibits the enzyme involved in its synthesis

Pass Criteria:

  • 3 out of 5

 


Q9

Please describe how ingested iron is absorbed.

  • Most ingested iron is ferric (3+) but the ferrous (2+) form is absorbed.
  • Minimal absorption in stomach but gastric secretions dissolve iron and aid conversion to the ferrous form.
  • Almost all absorption in duodenum. Iron is transported into enterocytes via DMT1.
  • Some stored as ferritin.
  • Remainder transported out via ferroportin 1 (basolateral transporter) in the presence of hephaestin.  Then converted to ferric form and bound to transferrin.
  • Dietary heme is absorbed by an apical transporter andiron is removed from the porphyrin in cytoplasm.

What are the mechanisms that regulate iron absorption?

Precise mechanisms uncertain, probably related to:

  • Recent dietary intake of iron.
  • State of body iron stores.
  • State of erythropoiesis in bone marrow.
  • The regulatory mechanisms are unclear

 


Q10

What factors influence the level of free calcium in plasma?

  • Protein binding – depends on plasma protein level and pH.
  • Total body calcium
    • bound in bone; bone calcium readily exchangeable or slowly exchangeable (resorption / deposition)
    • Intake
    • GI absorption under influence of vitamin D
    • Renal excretion under vitamin D influence
    • Parathyroid hormone
    • Calcitonin

How does bone resorption occur?

  • Osteoclasts are monocytes that develop from stromal cells under influence of RANKL.
  • Attach to bone via integrins in sealing zone of the membrane.
  • Hydrogen dependent proton pumps move into cell and acidify the area.
  • Acid dissolves hydroxyapatite and collagen.
  • Products move across osteoclast into interstitial fluid

 


Q11

How is carbon dioxide transported in the blood?

  • CO2 is carried in the blood as dissolved, as bicarbonate, and in combination with proteins as carbamino compounds

Draw and label the carbon dioxide dissociation curve.

other 2

 


Q12

What are the functions of serotonin?

a)            Regulation of vomiting reflex
b)            Regulation of mood
c)            Control of respiration
d)            Platelet aggregation and smooth muscle contraction
e)            Facilitate GI secretion and peristalsis
f)             Regulation of circadian rhythms
Core knowledge in bold

What are the steps in synthesis and catabolism of serotonin?

a)      Hydroxylation and decarboxylation of tryptophan to form serotonin

b)      Released serotonin from serotonergic neurones is recaptured by an active re-uptake mechanism and inactivated by MAO to form 5HIAA

c)       (5-hydroxyindoleacetic acid)

d)      5HIAA is excreted as a urinary metabolite

Core knowledge in bold

 


Q13

Please describe the withdrawal reflex.
Prompt: What happens if a painful stimulus is applied to the left lower limb of a normal person?

  • Reflex arc consisting of sensory organ(s)
    • afferent limb(s)
    • central integrator(s)
    • efferent limbs
    • effectors
    • Sensory organs are nociceptors in the skin or subcutaneous tissues, responding to noxious (usually painful) stimuli.
    • Afferent limb is/are sensory (pain) fibre(s) to the dorsal root, then dorsal horn of the spinal cord.
    • Central integrator consists of polysynaptic connections in the spinal cord.
    • Efferent limbs are motor nerves to effector muscles on the ipsi- and contralateral sides.
    • Effectors are muscles of the ipsi- and contralateral sides, which produce flexion and withdrawal of the ipsilateral limb and (crossed) extension of the opposite limb.

What are the important characteristics of polysynaptic reflexes?

The reflex effect becomes stronger and more prolonged the greater the stimulus. Due to:

  • The impulse arriving at effectors at different times due to interneurones.
  • Irradiation of the impulse up and down the spinal cord.
  • Recruitment of motor units.
  • Reverberation of the circuit as some interneurons turn back on themselves.

Above effects result in after-discharge due to continued bombardment of motor neurones by impulses arriving by complicated and circuitous paths.

What is meant by the term prepotency of the withdrawal reflex?

The reflex pre-empts spinal pathways from any other reflex activity occurring at the same time.

To pass: Magnified response

 


Q14

What are the thermoregulatory responses to cold?

Autonomic, Somatic, Endocrine and Behavioural

Response to Cold:

Increase heat production

Shivering

Hunger

Increased voluntary activity

Increased secretion Adrenaline and NA

Decrease heat loss

Cutaneous vasoconstriction

Curling up

Horripilation (pilo erection)

Pass: Shivering, Cutaneous vasconstriction

What are the thermoregulatory responses to heat?

Response to Heat:

Increase heat loss

Cutaneous vasodilation Sweating

Increased respiration

Decrease heat production Anorexia

Apathy and inertia

Pass: Any 2 from list

Where are these responses regulated?

Reflex response to cold controlled in post hypothalamus

Reflex response to heat controlled in ant hypothalamus

Afferents come from sensory receptors in skin, deep tissue, spinal cord, extrahypothalamic parts of brain and hypothalamus itself.

Pass: Hypothalamus

 


Q15

Name the principal hormones associated with regulation of Ca metabolism.

  1. 1,25 dihydroxy cholecalciferol
  2. Parathyroid hormone
  3. Calcitonin

Need 2 to pass

Describe the action of parathyroid hormone.

PTH-reabsorption of Ca from Bone; increase urine Phosphate excretion. Increase formation of 1,25 dihyrdroxycholecalciferol –> incre Ca absorption in GIT. Increased PO4 stimulate PM prod’n by lowering serum Ca and inhibit form of 1,25

DIHYDRO

Pass: Need 2 of 3

Describe the action of 1, 25 dihydroxycholecalciferol & calcitonin.

1,25 dihydrox —increase Ca and Phosphate absorption from intestine via calbindin proteins. Also increase Ca reabsorption in Kidneys, increase synthetic activity of osteoblasts, necessary for normal Ca of bony matrix.

Prompt: Only if doing well
Calcitonin- inhibits bone resorption (inhibits osteoclastic activity) -> lowers serum Ca AND PO4 levels. Increases Ca excretion in urine. Parafiollicular cells.

Need 1 point to pass

 


Q16

How do cells communicate one to the other?

Cell to cell via gap junctions. Chemical messengers in ECF: neural (neurotransmitters at synapses), endocrine (hormones and growth factors), paracrine (products of cells diffuse to neighbours), Autocrine = cell secretes messenger that acts on itself. Same chemical can function in several ways. Juxtacrine = molecules attached to membrane that attaches to another cell.

How do receptors respond to variations in messengers?

Receptors change with physiological variations: messenger in excess -> decrease receptors (down regulation, internalisation, desensitisation); deficient messenger -> increase receptors (up regulatoin). Exception is Angiotensin 11 in adrenal cortex.

How do messengers act?

Via ion channels (Ach, nicotinic, noradrenalin.); transcription of mRNAs (steroids, thyroid hormone.); activation of phospholipase C (angiotensin 11, noradrenalin. vasopressin); production of cAMP (noradrenalin); production of cGMP; increased activity tyrosine kinase (insulin); increased activity serine or threonine kinase (TGF, MAPK).

 


Q17

Describe the mechanisms of transport across cell membranes?

Exocytosis, endocytosis, ion channels, Carrier proteins, primary and secondary active transport.
Exo: ER to Golgi apparatus to granules/vesicles to cell membrane. Endo: phagocytosis, pinocytosis = liquid.

Give an example of active transport.

Ion channels open, voltage gated, ligand (molecule) gated. Transport proteins for active transport (vs chemical, electrical gradient), facilitated diffusion; uniports for one substance, symports require two together (eg Na + glucose), antiports exchange one for another (eg Na for K).

 


Q18

What are the phases of protein synthesis?

Transcription of mRNA; post transcriptional modification of mRNA; translation of mRNA to AA chain along a ribosome using tRNA; post translational modification of the protein in endoplasmic reticulum by hydroxylation, carboxylation, glycosylation, phosphorylation, cleavage and folding.

Describe the process of secretion of proteins from cells.

Polypeptide sequences are cleaved off, eg prohormones to hormones. Some proteins have leader sequences that target endoplasmic reticulum and are secreted by exocytosis. Others are secreted from cytoplasm via ATP dependent membrane transporters.

 


Q19

Describe the regulation of normal body temperature.

Hypothalamus controls range; circadian and ovulatory variations. Posterior responds to cold, anterior to heat. Heat production: activity, feeding, adrenaline drive, thyroid activity; shivering, vasoconstriction.

Heat losses: conduction, radiation, convection, vaporisation; sweating, vasodilation, increased respiration,

How is fever generated?

Pyrogens etc ‘reset the thermostat’
Cytokines are endogenous pyrogens

 


Q20

Describe the neurological pathways involved in normal micturition.

  • Spinal reflex mediated by S2, S3 and S4 nerve roots. Facilitated and inhibited by high centres; subject to voluntary control
  • First urge to void at 150mL. Marked fullness at 400mL – sudden rise in intra-vesicle pressure triggers reflex contraction.
  • Micturition reflex – stretch receptors in bladder wall. Afferent limb in pelvic nerves.
  • Parasympathetic efferent fibres (via same pelvic nerves) mediate contraction of detrusor muscle
  • Pudendal nerve (S2, S3 and S4) permits voluntary contraction of perineal muscles/external urethral sphincter, to slow or halt flow.
  • Sympathetic nerves to bladder play no role in micturition.

Pass Criteria:

  • Spinal Reflex
  • Parasympathetic control
  • Higher centre control

Describe the muscles involved in micturition.

  1. Bladder
    • Smooth muscle arranged in spiral, longitudinal and circular bundles.
    • Circular bundle is called the detrusor muscle. Contraction of detrusor is responsible for involuntary emptying. 
  2. External Urethral Sphincter
    • Skeletal muscle sphincter of the membranous urethra
    • Relaxes during micturition.
    • This is voluntarily controlled.
  3. Perineal muscles
    • Relaxes during micturition.
    • Also voluntarily controlled.
  4. In males, urine left in urethra expelled by several contractions of bulbocavernosus muscle.
  5. Contraction of abdominal wall muscles aids expulsion of urine
  • Note – Internal urethral sphincter (smooth muscle bundles passing on either side of urethra) play no apparent role in micturition.

Pass Criteria:

  • Bold to pass

What prevents vesico-ureteric reflux?

  • Oblique passage of ureters through bladder wall keeps ureters closed except during peristaltic waves

Pass Criteria:

  • Bold to pass

 


Q21

Where in the body is Ca2+ stored?

  • Bone: 99%
  • Plasma – bound to protein
  • Plasma – unbound (free/ionised) – important second messenger and is required for coagulation, nerve function and muscle contraction

Pass Criteria:

  • Bold to pass

How is the plasma Ca2+ level regulated?

PROMPT – What hormones increase or decrease plasma Calcium?

  • Parathyroid Hormone
    • Increases plasma Ca2+ by mobilising Ca2+ from bone
    • Increases Ca2+ reabsorption in kidney
    • Increases formation of 1,25-dihydroxycholecalciferol in the kidney
  • 1,25-dihydroxycholecalciferol
    • Increases Ca2+ absorption from intestine and kidneys
  • Calcitonin (from thyroid)
    • Lowers circulating Ca2+ levels
    • Effect by inhibition of bone reabsorption
    • It also increases Ca2+ excretion in urine
  • Glucocorticoids
    • Decrease plasma Ca2+ by inhibition osteoclast formation and activity
  • Oestrogens
    • Inhibit stimulatory effects of cytokines on osteoclasts
  • Growth Hormone
    • Increases Ca2+ excretion in urine & absorption in intestine
    • Net balance may be positive
  • Hypercalcaemia is a complication of cancer.
  • Raised Ca2+ from either:
    • bone erosion (local osteolytic hyperCa2+)
    • elevated Parathyroid hormone related protein (PTHrP)

Pass Criteria:

  • Bold and their effects on plasma Ca2+ (increase/decrease)

How does bone resorption occur?

  • Osteoclasts are monocytes that develop from stromal cells under influence of RANKL (receptor activator of nuclear factor kappa B ligand)
    • Attach to bone via integrins in sealing zone of the membrane
    • Hydrogen dependent proton pumps move into cell and acidify the area
    • Acid dissolves hydroxyapatite and acid proteases break down collagen
    • Products move across osteoclast into interstitial fluid

Pass Criteria:

  • Osteoclasts + 1 other

 


Q22

By what processes does the body lose heat?

  • Radiation & Conduction (70% of loss at 21°C)
  • Vaporisation of sweat (27%)
  • Respiration (2%)
  • Urination & defecation (1%)

Pass Criteria:

  • Bold to pass

How does the body produce heat?

  • Basal metabolic processes
  • Food intake

Pass Criteria:

  • Bold to pass

What temperature-regulating mechanisms are activated by the cold?

  • Muscular activity
  • Shivering
  • Hunger
  • Increased voluntary activity
  • Increased secretion of adrenaline & noradrenaline
  • Decreased heat loss mechanism
  • Cutaneous vasoconstriction
  • Curling up
  • Horripilation

Pass Criteria:

  • 4 to pass

What part of the brain controls the reflex responses activated by cold?

  • The posterior hypothalamus

 


Q23

Define the term 'referred pain'.

  • Irritation of a visceral organ causing pain in a distant somatic structure.

Pass Criteria:

  • Bold to pass

From which structure is pain referred to the shoulder?

  • Diaphragm

Pass Criteria:

  • Bold to pass

Explain this relationship.

  • Dermatome rule. Referred pain is usually to a structure that developed from the same embryonic segment or dermatome as the structure from which the pain originates.

Pass Criteria:

  • Bold to pass

Can you give another example of referred pain?

  • Cardiac pain to arm
  • Ureteric pain to testicle

Pass Criteria:

  • 1 to pass

What is the physiological basis/theory for referred pain?

  • Convergence-Projection Theory
    • Somatic and visceral pain fibres converge on the same second-order neurons in dorsal horn that then go onto thalamus and sensory cortex via common path.
    • Sensory cortex cannot determine whether the stimulus came from viscera or are of referral.

Pass Criteria:

  • 1 to pass

 


Q24

Where is thirst regulated?

  • Hypothalamus – diencephalon

Pass Criteria:

  • Bold to pass

What factors increase thirst?

  1. Increase in osmotic pressure in plasma sensed by osmoreceptors in the anterior hypothalamus
  2. Decrease in ECF volume (e.g. haemorrhage)
    • Sensed by baroreceptors in heart and blood vessels – increases thirst
    • Increase in renin – causes increase AT II – acts on the diencephalon neurons – increases thirst
  3. Psychological e.g. acute psychosis
  4. Others
    1. Increase liquids during eating (prandial drinking)
    2. Other poorly understood mechanisms such as increased osmolality as food absorbed and GI hormones acting on the hypothalamus

Pass Criteria:

  • Bold with understanding

In what situations may thirst sensation be blunted?

  • Hypothalamic disease
  • Direct damage to the diencephalon
  • Altered mental state
  • Psychosis
  • Lesion of the anterior communicating artery (supplies the hypothalamus)
  • Diet high in protein (products of protein metabolism cause water diuresis)

Pass Criteria:

  • Bold + 1 other