General physiology Flashcards
Where are temperature-sensitive receptors found in the body?
Anterior hypothalamus
What happens as a result of activation of heat-sensitive neurons?
Skin vasodilatation
Sweating
What happens as a result of activation of cold-sensitive neurons?
Inhibition of heat-sensitive neurons
Vasoconstriction
Shivering
Where are receptors found on internal surfaces/organs?
Respiratory and GI tracts
E.g. inhaling cold air causes shivering during inspiration, eating hot food causes sweating and vasodilatation
What is CORE temperature?
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
What is peripheral temperature?
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)
Definition of hypothermia
When core temp <35 deg
Symptoms of hypothermia
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
Factors affecting thermoregulation
Anaesthetics Exercise Circulatory shock Spinal injuries Hyper/hypoT4 Neonates and premature babies
How does anaesthetics affect thermoregulation?
Depress hypothalamic function
Vasodilatation with increased heat loss
Lack of shivering
Consequently drop in body temp
How does exercise affect thermoregulation?
Increase body temp
Hypothalamus cannot launch responses that result in loss of heat faster than its production from muscle metabolism
How does circulatory shock affect thermoregulation?
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
How do spinal injuries affect thermoregulation?
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
How does hyperT4 affect thermoregulation?
Increased BMR and O2 consumption
Patient hyperactive
All of the above contribute to increased temp
Patient intolerant of heat and feels cold
How does hypoT4 affect thermoregulation?
Opposite effects to hyperT4
Patient feels cold, intolerant of hot weather
Body temp low
Thermoregulation of neonates and premature babies
Large surface area to body weight ratio Inability to shiver Less insulating fat Temp regulating mechanisms less developed Thus predisposed to increased heat loss
In healthy adults, how many % does water constitute?
~60% of body weight
Components of body water
Intracellular
Extracellular: intravascular, extravascular (interstitial)
For a 70kg man, how much water would there be in each compartment?
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)
2 types of diuresis
Water
Osmotic
When does osmotic diuresis occur?
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)
How much water is gained from oxidation of metabolites?
About 300mL in 24 hours
In what ways is water lost?
Evaporation through respiratory system: 500mL Insensible losses through skin: 400mL Faeces: 100mL Urine: 500mL Total ~1500mL
How much solutes must be excreted each day in urine?
~600mOsmol
What is the maximal achievable urinary osmolality?
About 1200mOsmol/L
In health, why is thirst not experienced until ADH release has ensured that ingested water is retained by the kidneys?
Thirst receptors have a higher osmotic threshold of ~10mOsmol higher than osmoreceptors involved in ADH release
Mechanisms available for stimulation of thirst and ADH release in conditions where circulating blood volume falls
Reduced arterial BP (signals via carotid and aortic baroreceptors)
Reduced CVP (signals via atrial low pressure receptors)
Increased angiotensin II in brain
Causes of pure water depletion
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
Maximal excretory rate of kidneys
~750mL of water per hour
Causes of water intoxication
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
What is the major cation in ECF?
Sodium
How much Na is consumed in a typical daily diet?
100-300mmol
Almost all absorbed from GI tract. Only ~5-10mmol daily lost in faeces
Ways of Na excretion
Mainly renal
Skin through sweat (very variable)
How much Na does each litre of sweat contain?
30-50mmol of Na
Where is Na reabsorbed in the kidneys?
99% of filtered Na reabsorbed:
65% in proximal tubule
25% in loop of Henle
~10% in distal tubules and colelcting ducts
Renal mechanisms of regulation of Na balance
GFR
Renin-angiotensin mechanism
Several prostaglandins
Important intrarenal effects of angiotensin II
Stimulate Na reabsorption in most nephron segments
CONSTRICT glomerular arterioles
These favour Na retention and restoration of ECF volume
Extrarenal mechanisms of regulation of Na balance
Renin-angiotensin mechanism via aldosterone
ANP (released from cardiac atria in response to stretch)
In which parts of the body does aldosterone promote Na reabsorption?
Distal tubule and collecting ducts of kidneys
Colonic epithelium
Ducts of salivary and sweat glands
Mechanism of action of ANP
Increase Na excretion by:
Increasing GFR
Inhibiting Na reabsorption in collecting ducts
Reducing secretion of renin and aldosterone
Causes of hyperNa
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
Loss of Na leads to loss of water at a rate of…?
1L per 150mmol of Na
Water loss is shared between plasma and extravascular ECF
What is the major intracellular cation?
Potassium (98% within cells)
Intracellular concentration ~150mmol/L
Causes of hyperK
Excess administration of K esp rapidly Renal failure Haemolysis Crush injuries Tissue necrosis e.g. burns, ischaemia Metabolic acidosis Adrenal insufficiency (Addison's)
ECG changes in hyperK
Tall, tented T waves
Loss of P waves
Widening of QRS complex
Management of hyperK
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
Causes of hypoK
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)
Symptoms and signs of hypoK
Clinical fatigue and lethargy with eventual muscle weakness
ECG changes in hypoK
Low, broad T waves
U waves
Prolonged PR and QT intervals
Management of hypoK
Replacement with oral supplements (Sando-K)
Slow IV replacement with careful monitoring if severe
Important buffer systems in the body
Proteins
Hb
Phosphate
Bicarbonate
Carbonic acid-bicarbonate system
H2O + CO2 –> H2CO3- –> HCO3-
catalysed by carbonic anhydrase
Henderson-Hasselbach equation
pH = pK + log [HCO3-]/[H2CO3] = 6.1 + log [HCO3-]/(0.03 x pCO2)
= constant + kidney function/lung function
pK = 6.1
Daily fluid requirements of a healthy person
2.5-3L IV fluid containing
150mmol of Na
60mmol of K
Physiological responses after surgery/trauma
Increased catecholamines
Increased secretion of cortisol and aldosterone
Na and water retention by kidneys
Reduction of urine volume and Na concentration
Causes of fluid loss in surgical patients
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
Why does hypovolaemia occur in septic shock?
Large increase in capillary permeability causing extensive loss of proteins and electrolytes into extracellular space
Peripheral vasodilatation
Fluid loss in sepsis can be monitored by:
Urine output
Blood pressure
CVP
Pulmonary wedge pressure monitoring
Types of colloids (for volume expansion)
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)
Uses of 20% albumin
For replacement of plasma proteins:
In severe hypoproteinaemia in renal or liver disease
After large-volume paracentesis
After massive liver resection
What is dextran?
Glucose polymers of different molecular weights
Interferes with cross-matching and coagulation (decreases factor VIII, inhibits plt aggregation)
What are gelatins?
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
What is polygeline (Haemaccel)?
Contains K and Ca
Can cause coagulation if mixed with citrated blood in giving set
Stays shorter time in circulation
What is succinylated gelatin (Gelofusin)?
Larger molecular weight than polygeline, hence slightly longer effect
Does NOT contain Ca
What is Hetastarch (Hespan)?
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
What is Pentastarch (Pentaspan)?
Lower degree of protection from metabolism
Shorter-lasting effects than Hetastarch
Which plasma expander is most advantageous in ACUTE hypovolaemia?
Gelofusin
Short-acting, cheap
No Ca hence does not cause coagulation if mixed with citrated blood in giving set
Which plasma expander is most advantageous in CHRONIC hypovolaemia?
Hetastarch (Hespan)
Longer-acting
Larger molecules better retained in circulation when capillaries leaky e.g. septic shock
High degree of protection from metabolism
General problems of plasma expanders
Dilution coagulopathy
Allergic reactions
Interfering with cross-matching (dextran 70)
Persistence of colloid effect dependent on molecular sie and protection from metabolism
Composition of 0.9% sodium chloride
Na 155 K 0 Ca 0 Cl- 155 Bicarb 0 Osmolality 309 mOsmol/L
Composition of Hartmann’s solution
Na 131 K 5 Ca 2 Cl- 111 Bicarb 29 Osmolality 280 mOsmol/L
Composition of 5% dextrose
0 all electrolytes
Osmolality 278 mOsmol/L
Composition of 1.26% Na bicarbonate
Na 150 K 0 Ca 0 Cl- 0 Bicarb 150 Osmolality 300mOsmol/L
What is the distribution of crystalloids when they are initially infused?
1/3 stays in INTRAvascular compartment
2/3 passes into ECF
Safety rules for giving IV KCl to supplement K+ in crystalloid fluids
Urine output of ≥40mL/hr
≤40mmol added to 1L of fluid
Infusion rate ≤40mmol/hr
Definition of oedema
Increase in INTERSTITIAL fluid volume above normal levels
2 types of pressures influencing oedema
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
What is the Starling equilibrium?
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)
Starling equilibrium across capillary
FILTRATION favoured at ARTERIAL end of capillary
ABSORPTION favoured at VENOUS end
What happens to the fluid not reabsorbed from the interstitium by capillaries?
Returned to the circulation by the lymphatic system
Causes of oedema
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
Causes of lymphatic obstruction
Surgical removal of lymph node e.g. axillary clearance with mastectomy or block dissection
Metastatic tumours
Irradiation
Filariasis
Why is hypoK commonly associated with metabolic alkalosis?
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
3 mechanisms of hypoK leading to metabolic alkalosis
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.
