General physiology

Question 1

Where are temperature-sensitive receptors found in the body?

Answer 1

Anterior hypothalamus

Question 2

What happens as a result of activation of heat-sensitive neurons?

Answer 2

Skin vasodilatation

Sweating

Question 3

What happens as a result of activation of cold-sensitive neurons?

Answer 3

Inhibition of heat-sensitive neurons
Vasoconstriction
Shivering

Question 4

Where are receptors found on internal surfaces/organs?

Answer 4

Respiratory and GI tracts

E.g. inhaling cold air causes shivering during inspiration, eating hot food causes sweating and vasodilatation

Question 5

What is CORE temperature?

Answer 5

Maintained between 36-37.5 degrees

Temp of thoracic, abdominal contents and brain
Usually measured as RECTAL temperature (0.5deg higher than mouth/axilla)
Shows DIURNAL variation (higher in evening than early morning)
Varies during MENSTRUAL cycle: 0.5deg higher in LATTER HALF

Question 6

What is peripheral temperature?

Answer 6

Less than core temp, heat being lost from surface to environment
Heat is lost through: conduction and evaporation from skin to air, convection from skin due to air movement; from lungs via convection of tidal air flow, radiation from naked skin (and between layers of clothing)

Question 7

Definition of hypothermia

Answer 7

When core temp <35 deg

Question 8

Symptoms of hypothermia

Answer 8

32-35 deg: shivery, feeling cold

<32 deg (often fatal): bradycardia, hypotension, resp depression, muscle stiffness, metabolic abnormalities

Death often from cardiac arrhythmias, esp. VF

Question 9

Factors affecting thermoregulation

Answer 9

Anaesthetics
Exercise
Circulatory shock
Spinal injuries
Hyper/hypoT4
Neonates and premature babies

Question 10

How does anaesthetics affect thermoregulation?

Answer 10

Depress hypothalamic function
Vasodilatation with increased heat loss
Lack of shivering
Consequently drop in body temp

Question 11

How does exercise affect thermoregulation?

Answer 11

Increase body temp

Hypothalamus cannot launch responses that result in loss of heat faster than its production from muscle metabolism

Question 12

How does circulatory shock affect thermoregulation?

Answer 12

Reduced tissue perfusion
Reduced cellular metabolism and heat production
Results in decreased body temp
Compensatory mechanisms include vasoconstriction, piloerection and increased secretion of CATECHOLAMINES
Skin feels COLD

Exception is SEPTIC (endotoxic) shock - where there is vasodilation and skin feels hot

Question 13

How do spinal injuries affect thermoregulation?

Answer 13

Thermoregulatory mechanisms lost below level of injury
Vasoconstriction lost, hence heat loss increased
Patient unable to shiver
Sweating in relation to hyperthermia lost below level of lesion
Quadriplegics tend to assume temp of environment

Question 14

How does hyperT4 affect thermoregulation?

Answer 14

Increased BMR and O2 consumption
Patient hyperactive
All of the above contribute to increased temp
Patient intolerant of heat and feels cold

Question 15

How does hypoT4 affect thermoregulation?

Answer 15

Opposite effects to hyperT4
Patient feels cold, intolerant of hot weather
Body temp low

Question 16

Thermoregulation of neonates and premature babies

Answer 16

Large surface area to body weight ratio
Inability to shiver
Less insulating fat
Temp regulating mechanisms less developed
Thus predisposed to increased heat loss

Question 17

In healthy adults, how many % does water constitute?

Answer 17

~60% of body weight

Question 18

Components of body water

Answer 18

Intracellular

Extracellular: intravascular, extravascular (interstitial)

Question 19

For a 70kg man, how much water would there be in each compartment?

Answer 19

28L INTRAcellular (60-65%)

14L EXTRAcellular (35-40%):
3L in blood PLASMA (5%)
10L INTERSTITIAL (24%)
1L TRANSCELLULAR (3%)
(e.g. CSF, peritoneal, intraocular fluid)

Question 20

2 types of diuresis

Answer 20

Water

Osmotic

Question 21

When does osmotic diuresis occur?

Answer 21

When more solute is presented to the tubules than they can reabsorb

e.g. diabetes, administration of mannitol (filtered, but non-reabsorbable solute), inhibition of tubular function (e.g. by drugs blocking NaCl reabsorption)

Question 22

How much water is gained from oxidation of metabolites?

Answer 22

About 300mL in 24 hours

Question 23

In what ways is water lost?

Answer 23

Evaporation through respiratory system: 500mL
Insensible losses through skin: 400mL
Faeces: 100mL
Urine: 500mL
Total ~1500mL

Question 24

How much solutes must be excreted each day in urine?

Answer 24

~600mOsmol

Question 25

What is the maximal achievable urinary osmolality?

Answer 25

About 1200mOsmol/L

Question 26

In health, why is thirst not experienced until ADH release has ensured that ingested water is retained by the kidneys?

Answer 26

Thirst receptors have a higher osmotic threshold of ~10mOsmol higher than osmoreceptors involved in ADH release

Question 27

Mechanisms available for stimulation of thirst and ADH release in conditions where circulating blood volume falls

Answer 27

Reduced arterial BP (signals via carotid and aortic baroreceptors) Reduced CVP (signals via atrial low pressure receptors) Increased angiotensin II in brain

Question 28

Causes of pure water depletion

Answer 28

Reduced oral intake: exhaustion, inability to swallow (e.g. comatose, confusion), restricted intake after GI surgery Renal causes: osmotic diuresis, diuretic phase of acute renal failure, post-relief of obstructive uropathy, diabetes insipidus Loss of fluid from lungs Hyperventilation from unhumidified air Others: fever, burns, diarrhoea, fistulae

Question 29

Maximal excretory rate of kidneys

Answer 29

~750mL of water per hour

Question 30

Causes of water intoxication

Answer 30

Impaired renal excretion of water: renal failure with excessive intake (commonest cause in surgical practice), excessive administration of 5% dextrose in post-op period where ADH secretion is high, ADH-secreting tumours Cardiac failure Liver disease Hypoalbuminaemia

Question 31

What is the major cation in ECF?

Answer 31

Sodium

Question 32

How much Na is consumed in a typical daily diet?

Answer 32

100-300mmol Almost all absorbed from GI tract. Only ~5-10mmol daily lost in faeces

Question 33

Ways of Na excretion

Answer 33

Mainly renal | Skin through sweat (very variable)

Question 34

How much Na does each litre of sweat contain?

Answer 34

30-50mmol of Na

Question 35

Where is Na reabsorbed in the kidneys?

Answer 35

99% of filtered Na reabsorbed: 65% in proximal tubule 25% in loop of Henle ~10% in distal tubules and colelcting ducts

Question 36

Renal mechanisms of regulation of Na balance

Answer 36

GFR Renin-angiotensin mechanism Several prostaglandins

Question 37

Important intrarenal effects of angiotensin II

Answer 37

Stimulate Na reabsorption in most nephron segments CONSTRICT glomerular arterioles These favour Na retention and restoration of ECF volume

Question 38

Extrarenal mechanisms of regulation of Na balance

Answer 38

Renin-angiotensin mechanism via aldosterone | ANP (released from cardiac atria in response to stretch)

Question 39

In which parts of the body does aldosterone promote Na reabsorption?

Answer 39

Distal tubule and collecting ducts of kidneys Colonic epithelium Ducts of salivary and sweat glands

Question 40

Mechanism of action of ANP

Answer 40

Increase Na excretion by: Increasing GFR Inhibiting Na reabsorption in collecting ducts Reducing secretion of renin and aldosterone

Question 41

Causes of hyperNa

Answer 41

``` Na excess: Excessive IV sodium therapy esp post-op Conn's syndrome Cushing's Steroid therapy Chronic CCF Liver cirrhosis ``` Water depletion: Reduced water intake: coma, confusion Renal causes: osmotic diuresis, diuretic phase of AKI, DI Others: fever, burns, diarrhoea, fistulae

Question 42

Loss of Na leads to loss of water at a rate of...?

Answer 42

1L per 150mmol of Na Water loss is shared between plasma and extravascular ECF

Question 43

What is the major intracellular cation?

Answer 43

Potassium (98% within cells) Intracellular concentration ~150mmol/L

Question 44

Causes of hyperK

Answer 44

``` Excess administration of K esp rapidly Renal failure Haemolysis Crush injuries Tissue necrosis e.g. burns, ischaemia Metabolic acidosis Adrenal insufficiency (Addison's) ```

Question 45

ECG changes in hyperK

Answer 45

Tall, tented T waves Loss of P waves Widening of QRS complex

Question 46

Management of hyperK

Answer 46

10mL 10% calcium gluconate Insulin + dextrose infusion (10 units of Actrapid in 100mL of 20% glucose) Salbutamol Ion-exchange resins e.g. Ca resonium oral/rectal (Ca exchanged for K, which is then lost in faeces, takes 24hr to work, inappropriate in emergency) Haemodialysis

Question 47

Causes of hypoK

Answer 47

Inadequate intake: K-free IV fluids, reduced oral intake (coma, dysphagia) Excessive losses: 1) Renal losses: diuretics, renal tubular disorders 2) GI losses: diarrhoea, vomiting, fistulae, laxatives, villous adenoma 3) Endocrine: Cushing's, steroid therapy, hyperaldosteronism (primary and secondary)

Question 48

Symptoms and signs of hypoK

Answer 48

Clinical fatigue and lethargy with eventual muscle weakness

Question 49

ECG changes in hypoK

Answer 49

Low, broad T waves U waves Prolonged PR and QT intervals

Question 50

Management of hypoK

Answer 50

Replacement with oral supplements (Sando-K) | Slow IV replacement with careful monitoring if severe

Question 51

Important buffer systems in the body

Answer 51

Proteins Hb Phosphate Bicarbonate

Question 52

Carbonic acid-bicarbonate system

Answer 52

H2O + CO2 --> H2CO3- --> HCO3- catalysed by carbonic anhydrase

Question 53

Henderson-Hasselbach equation

Answer 53

pH = pK + log [HCO3-]/[H2CO3] = 6.1 + log [HCO3-]/(0.03 x pCO2) = constant + kidney function/lung function pK = 6.1

Question 54

Daily fluid requirements of a healthy person

Answer 54

2.5-3L IV fluid containing 150mmol of Na 60mmol of K

Question 55

Physiological responses after surgery/trauma

Answer 55

Increased catecholamines Increased secretion of cortisol and aldosterone Na and water retention by kidneys Reduction of urine volume and Na concentration

Question 56

Causes of fluid loss in surgical patients

Answer 56

Blood: trauma, surgery Plasma: burns GI: NG aspiration, D+V, intestinal obstruction, paralytic ileus, fistulae, stomas Exudate in peritoneal cavity: peritonitis, acute pancreatitis, septicaemia Excess insensible losses: fever, sweating, hyperventilation

Question 57

Why does hypovolaemia occur in septic shock?

Answer 57

Large increase in capillary permeability causing extensive loss of proteins and electrolytes into extracellular space Peripheral vasodilatation

Question 58

Fluid loss in sepsis can be monitored by:

Answer 58

Urine output Blood pressure CVP Pulmonary wedge pressure monitoring

Question 59

Types of colloids (for volume expansion)

Answer 59

Short-term: 1) DEXTRAN: dextran 70 in 0.9% saline or 5% glucose 2) GELATIN: polygeline (Haemaccel), succinylated gelatin (Gelofusin) Medium-term: 1) Human ALBUMIN solution (5%, 20%) 2) PENTASTARCH (Pentaspan) Long-term: HYDROXYETHYL STARCH: hetastarch (Hespan)

Question 60

Uses of 20% albumin

Answer 60

For replacement of plasma proteins: In severe hypoproteinaemia in renal or liver disease After large-volume paracentesis After massive liver resection

Question 61

What is dextran?

Answer 61

Glucose polymers of different molecular weights Interferes with cross-matching and coagulation (decreases factor VIII, inhibits plt aggregation)

Question 62

What are gelatins?

Answer 62

Prepared by hydrolysis of bovine collage Do not affect coagulation per se Low incidence of allergic reactions Small average particle size, hence stay in intravascular space for SHORTER period of time

Question 63

What is polygeline (Haemaccel)?

Answer 63

Contains K and Ca Can cause coagulation if mixed with citrated blood in giving set Stays shorter time in circulation

Question 64

What is succinylated gelatin (Gelofusin)?

Answer 64

Larger molecular weight than polygeline, hence slightly longer effect Does NOT contain Ca

Question 65

What is Hetastarch (Hespan)?

Answer 65

6% in saline Largest molecular weight of any plasma expander, hence stays in circulation longer Most useful in capillary leak May cause coagulopathy High degree of protection from metabolism

Question 66

What is Pentastarch (Pentaspan)?

Answer 66

Lower degree of protection from metabolism | Shorter-lasting effects than Hetastarch

Question 67

Which plasma expander is most advantageous in ACUTE hypovolaemia?

Answer 67

Gelofusin Short-acting, cheap No Ca hence does not cause coagulation if mixed with citrated blood in giving set

Question 68

Which plasma expander is most advantageous in CHRONIC hypovolaemia?

Answer 68

Hetastarch (Hespan) Longer-acting Larger molecules better retained in circulation when capillaries leaky e.g. septic shock High degree of protection from metabolism

Question 69

General problems of plasma expanders

Answer 69

Dilution coagulopathy Allergic reactions Interfering with cross-matching (dextran 70) Persistence of colloid effect dependent on molecular sie and protection from metabolism

Question 70

Composition of 0.9% sodium chloride

Answer 70

``` Na 155 K 0 Ca 0 Cl- 155 Bicarb 0 Osmolality 309 mOsmol/L ```

Question 71

Composition of Hartmann's solution

Answer 71

``` Na 131 K 5 Ca 2 Cl- 111 Bicarb 29 Osmolality 280 mOsmol/L ```

Question 72

Composition of 5% dextrose

Answer 72

0 all electrolytes | Osmolality 278 mOsmol/L

Question 73

Composition of 1.26% Na bicarbonate

Answer 73

``` Na 150 K 0 Ca 0 Cl- 0 Bicarb 150 Osmolality 300mOsmol/L ```

Question 74

What is the distribution of crystalloids when they are initially infused?

Answer 74

1/3 stays in INTRAvascular compartment | 2/3 passes into ECF

Question 75

Safety rules for giving IV KCl to supplement K+ in crystalloid fluids

Answer 75

Urine output of ≥40mL/hr ≤40mmol added to 1L of fluid Infusion rate ≤40mmol/hr

Question 76

Definition of oedema

Answer 76

Increase in INTERSTITIAL fluid volume above normal levels

Question 77

2 types of pressures influencing oedema

Answer 77

Hydrostatic pressure: causes flow from vessel to tissue space Plasma oncotic pressure: retention of plasma proteins within vasculature causes fluid to be retained in vessels

Question 78

What is the Starling equilibrium?

Answer 78

Describes relationship between hydrostatic, oncotic (colloid osmotic) pressures and fluid flow across capillary membrane Capillary hydrostatic pressure + tissue oncotic pressure (pressure driving fluid OUT of capillaries) = interstitial fluid pressure + plasma oncotic pressure (pressure holding fluids WITHIN capillaries)

Question 79

Starling equilibrium across capillary

Answer 79

FILTRATION favoured at ARTERIAL end of capillary ABSORPTION favoured at VENOUS end

Question 80

What happens to the fluid not reabsorbed from the interstitium by capillaries?

Answer 80

Returned to the circulation by the lymphatic system

Question 81

Causes of oedema

Answer 81

Increased capillary hydrostatic pressure: chronic right HF, venous obstruction, increased fluid volume (e.g. overtransfusion) Decreased plasma oncotic pressure due to hypoproteinaemia: starvation, cirrhosis, nephrotic syndrome Increased capillary permeability: inflammatory and allergic reactions Increased tissue oncotic pressure: lymphatic blockage, protein accumulation in burns

Question 82

Causes of lymphatic obstruction

Answer 82

Surgical removal of lymph node e.g. axillary clearance with mastectomy or block dissection Metastatic tumours Irradiation Filariasis

Question 83

Why is hypoK commonly associated with metabolic alkalosis?

Answer 83

2 factors: 1) Common causes of metabolic alkalosis (vomiting, diuretics) directly induce H+ and K loss (via aldosterone) and thus also cause hypoK 2) HypoK is a very important cause of metabolic alkalosis by 3 mechanisms

Question 84

3 mechanisms of hypoK leading to metabolic alkalosis

Answer 84

1) Initial effect = transcellular shift where K leaves and H+ enters the cells, thereby raising the extracellular pH 2) Transcellular shift in the cells of the PROXIMAL tubules resulting in an intracellular acidosis, which promotes ammonium production and excretion 3) In the presence of hypoK, hydrogen secretion in the PROXIMAL and DISTALtubules increases. This leads to further BICARB REABSORPTION. The net effect is an increase in the net acid excretion.