2009B13 Explain the physiological processes that cause oliguria in response to hypovolaemic shock.

 

List:

·     Definitions

·     Direct effect: pre-renal failure

·     Compensation

·     Kidney injury

 

Definitions:

Oliguria

·     <0.5mL/kg/h

Hypovolaemic shock

·     Reduced blood volume resulting in failure to meet tissue metabolic requirement

·     Occurs at ~20% blood loss

Cause of oliguria

·     ↓Filtration

·     ↑Reabsorption

·     Acute tubular necrosis (or whatever it is that causes intrinsic renal failure)

 

Direct effect: pre-renal failure:

Causal pathway

↓Blood volume -> ↓preload -> ↓cardiac output -> ↓mAP -> ↓Pc -> ↓GFR -> ↓UO

Relevant physiology

GFR = K[(PC – PB) – σ(πC – πB)]

·     Pc (capillary hydrostatic pressure) is the major variable in hypovolaemia

RBF = (mAP – CVP) / RVR

·     Effective autoregulation mAP 70-170mmHg

mAP – CVP = CO x TPR

·     Factors ↑CO: ↑preload, ↓afterload, ↑rate, ↑contractility

 

Compensatory response:

↑SNS

Stimulus: baroreceptor reflex

Effect:

·     Constrict efferent > afferent arterioles (α1)

·     Hence ↓GFR but preserved GFP

·     ↑ proximal tubular reabsorption of Na+/H2O (α1)

↑ renin release (see RAAS) (β1)

↑ADH

Source: hypothalamus -> posterior pituitary

Release stimuli:

·     Stress response from surgery

·     Many drugs

·     ↑osmolality (sensitive to ∆2%) – dehydration from pre-op fasting

·     ↓blood volume (sensitive to ∆10% but overrides osmolality)

·     ↓mAP

·     Angiotensin 2

Effects: ↑reabsorption

·     Insertion of aquaporin 2 into apical membrane of collecting ducts -> ↑H2O reabsorption

·     Insertion of urea transporters -> ↑ medullary interstitial osmolarity

·     ↑Na+ reabsorption in thick ascending loop of Henle

↑RAAS

Source: granular cell of juxtaglomerular apparatus

Release stimuli:

·     ↑SNS activation of granular cells (β1) - e.g. pain

·     ↓stretch of afferent arteriolar baroreceptors - i.e. hypotension

·     ↓ NaCl delivery to macula densa -> ↑PGE2, ↓adenosine release - i.e. ↓GFR

Effects of angiotensin 2:

·     Constrict efferent > afferent arterioles

·     Hence ↓GFR with preserved GFP

·     ↑Na+/H2O reabsorption from PT (via Na+/H+ exchange) (AGTR1)

·     ↑release of aldosterone

·     ↑release of ADH

Effects of angiotensin-3:

·     40% of pressor activity

·     100% of aldosterone induction

Effects of aldosterone:

·     ↑Na+ reabsorption from principal cells of connecting tubule and collecting ducts (MR)

·     Indirectly causes H2O reabsorption via ↑ECF osmolality hence ↑ADH

 

Kidney injury:

Cause

·     ↓mAP -> ischaemia -> ATN

·     ? Other factors