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


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


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


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


What are the physiological effects of dehydration?

Water loss lowers ECF and ICF leading to:

  • Decreased BP
  • Increased HR
  • Increased ADH
  • Decreased Urine Output
  • Decreased GFR
  • Increased Renin/Angiotensin
  • Increased thirst

This is all aiming to maintain IV volume.

Pass Criteria:

  • Bold with understanding of the concepts, especially with regard to movement of Na+.

Describe the effects of a rapid IV infusion of 1000 mL of Normal Saline.
Prompt: What is the cardiovascular effect you would see?

  • Increased Cl- and acidosis
  • Increased baroreceptor firing
  • Decreased HR
  • Increased BP
  • Increased Urine Output
  • Decreased Renin/Angiotensin
  • Improved capillary return

NB. Bainbridge reflex describes an initial increase in HR if slow initially.

Pass Criteria:

  • Bold plus one more.

What is an alternative physiological fluid replacement?

Hartmann’s (lactated Ringer’s) or Plasmalyte.

Pass Criteria:

  • Any 1 of the Bold.


What is the pathogenesis of fever?
Prompt: What causes a febrile response?
Prompt: Which area of the brain is activated in a febrile response?

  • Bacterial toxins (e.g. endotoxin) act on monocytes, macrophages, and Kupfer cells to produce cytokines that act as endogenous pyrogens
  • IL-1-beta, IL-6, IFN-Beta, IFN-Gamma, and TNF-alpha can act independantly to produce fever.
  • Cytokines also produced by cells in the CNS when these are stimulated by infection – may act directly on the thermoregulatory centres.
  • Activates the preoptic area of the hypothalamus
  • Causes release of prostaglandins (e.g. PGE2) which causes a raise in the temperature set point, resulting in a fever.

Pass Criteria:

  • Concept plus one more.

What is the body's response to hot and cold environments?
Prompt: What happens to heat production and loss?

Mechanisms activated by cold:

  • Increased heat production
    • Shivering
    • Hunger
    • Voluntary activity
    • Noradrenaline/Adrenaline release
  • Decreased heat loss
    • Skin vasoconstriction
    • Curling up
    • Horripilation

Mechanisms activated by heat:

  • Decreased heat production:
    • Anorexia
    • Apathy
    • Inertia
  • Increased heat loss
    • Cutaneous vasodilation
    • Sweating
    • Increased respiration

Pass Criteria:

  • 1 mechanism for each of heat production and loss for cold environment
  • 1 mechanisms for each of heat production and loss for hot environment


Describe the process by which extracellular fluid tonicity is regulated.
Prompt: Where is plasma osmotic pressure sensed?

  • An increase in plasma oncotic pressure causes an increase in thirst and is sensed by osmoreceptors in the anterior hypothalamus (mainly the organum vasculosum of the lamina terminalis)
  • Vasopressin (ADH) secretion from the posterior pituitary gland is stimulated, which stimulates renal V2 receptors and results in the insertion of water channels (aquaporins) in luminal membranes of renal collecting tubules, allowing more water to return to the body
  • Conversely, as plasma oncotic pressure falls (285 mosm/kg is the critical point) ADH secretion is suppressed.

Pass Criteria:

  • Thirst increases water intake and ADH reduces water excretion by the kidneys. Both of these lead to ECF dilution.
  • Bold and correct understanding of the concept.

What factors other than rising osmotic pressure increases vasopressin secretion?

  • Decreased ECF volume
  • Pain
  • Emotion
  • Surgical stress
  • Exercise
  • Nausea and vomiting
  • Standing
  • Angiotensin II
  • Medications (Clofibrate and Carbamazepine)

Pass Criteria:

  • Bold and 1 more to pass.