PATHOPHYSIOLOGY OF ACUTE KIDNEY

INJURY (AKI) CAUSED BY SHOCK

Presented by:
Moh. Faisal Riza
Artaria Tjempakasari
INTRODUCTION
Kidney
Excretion of waste materials and toxins from the body in the form of urine
• Regulation of blood volume and chemistry  excretion of dissolved substances
and water  selectively

Acute Kidney Injury (AKI) Sudden and severe decline in kidney filtration function.

Signs: Definite indicators of kidney damage:

• Increased concentration of serum creatinine or • Decreased urine production.
azotemia (elevated BUN concentration)
Acute kidney
Acute Kidney Failure (AKF) or Acute Renal Failure (ARF)
injury (AKI)

Incidence
last 15 years  increase in incidence.
The actual incidence within the community is much higher than recorded figures.

Global Incidence:

• 0.5-0.9% in the community,

• 0.7-18% in hospital patients,
• 20% in patients treated in the ICU.

Mortality rate:

• 25% to 80%.
 Shock Cases:
Severe renal hypoperfusion (mean arterial pressure < 70 mmHg)

Prolonged shock duration

Disrupted autoregulation mechanism
• Afferent arterioles experience vasoconstriction
• Mesangial contraction occurs
• Increased sodium and water reabsorption

Prerenal kidney failure or functional acute kidney failure

• No structural damage to the kidneys has occurred.
 DEFINITION

Acute kidney injury (AKI)

A syndrome characterized by impaired kidney function in regulating the body's fluid and
electrolyte composition, as well as excreting waste products of metabolism. This occurs suddenly
and rapidly, typically reversible, followed by kidney failure to excrete nitrogenous waste, with or
without disruption of fluid and electrolyte balance.

Basis of AKI Definition:

Serum creatinine (Cr) levels and urine production (urine output/UO).

Comparison Between Acute Kidney Injury, Acute Kidney Disease and
Chronic Kidney Disease.
Functional Changes
Disease Time Structural Damage
Change Limit
Increase in creatinine ≥1.5 times
Acute kidney
≤7 days from baseline (or an increase Urine volume <0.5 mL/kg for ≥6 hours Not definable.
injuriy
≥0.3 mg/dL within 48 hours)

eGFR <90 mL per minute (with markers

Increase in creatinine ≥1.5 times indicating damage)
Acute kidney <7 days to < 90
from baseline (or an increase Kidney Damage
disease days eGFR mL per minute per 1.73 m2 <60
≥0.3 mg/dL within 48 hours)
mL per minute

eGFR <90 mL per minute (with markers

Chronic kidney indicating damage)
≥90 days Not applicable Kidney Damage
disease eGFR mL per minute per 1.73 m2 <60
mL per minute

* Comparison in terms of timing, functional changes, and structural damage.

* Kidney damage can be assessed through pathology, urine or blood tests, or imaging. Structural criteria are not included in the current definition of
acute kidney injury as they have not yet been validated for this purpose.
AKI Staging according to the latest KDIGO definition (Ronco C et al, 2019)

Stage 1
Increase in creatinine ≥1.5 times from baseline or an increase ≥0.3 mg/dL
within 48 hours or urine volume <0.5 mL/kg in 6-12 hours.

Stage 2
Increase in creatinine ≥2.0 times from baseline or urine volume <0.5 mL/kg
for more than 12 hours.

Stage 3
Increase in creatinine ≥3.0 times from baseline or an increase ≥4.0 mg/dL
or acute dialysis or urine volume <0.5 mL/kg for ≥24 hours.
 ETIOLOGY
Disruption of oxygen and ✓ due to microcirculation disturbances

Causes of nutrient delivery to nephrons

AKI
Increased energy demands ✓ due to cellular-level stress

Category Abnormality Possible causes

Elevated intra-abdominal
pressure
Intravascular volume depletion
Peripheral vasodilation
Prerenal
Decreased cardiac output
Abdominal compartment syndrome
Bleeding, gastrointestinal disorders, kidney disorders, skin and mucosal
membrane abnormalities, nephrotic syndrome, cirrhosis, capillary leakage.
Sepsis, cirrhosis, anaphylaxis, pharmacological side effects.
Cardiogenic shock, pericardial disease, congestive heart failure, valvular
disease, lung disease, sepsis.

Renal vasoconstriction Early sepsis, hepatorenal syndrome, acute hypercalcemia, drug side
effects, iodinated contrast media.
Category Abnormality Possible causes

- Drug side effects

- Hematological disorders: hemolytic uremic syndrome, thrombotic
thrombocytopenic purpura
Glomerular injury - Inflammation: anti-glomerular basement membrane disease, antineutrophil
cytoplasmic antibody disease, infection, membranoproliferative
glomerulonephritis, immunoglobulin A nephropathy, systemic lupus
erythematosus, Henoch-Schönlein purpura, polyarteritis nodosa

Renal microvasculature
Malignant hypertension, pregnancy-related toxemia, hypercalcemia, contrast media,
scleroderma, drug side effects.
Renal
- Endogenous toxins: myoglobin, hemoglobin, paraproteinemia, uric acid.
Tubular injury - Exogenous toxins: antibiotics, chemotherapy agents, contrast media, phosphorus-
containing preparations.
- Ischemia due to hypoperfusion.

- Acute allergic interstitial nephritis.

Tubulointerstitial injury - Infections: Legionella, Leptospira, Rickettsia, Hantavirus, Candida, Plasmodium,
tuberculosis.
- Infiltration.

Vascular abnormalities
Arterial thrombosis, vasculitis, dissection, thromboembolism, venous thrombosis,
compression, trauma.
Category Abnormality Possible causes

Causes of lower urinary - Tubular injury

tract - Bladder: obstruction, calculi, carcinoma, infection (schistosomiasis)
- Functional: neurogenic bladder, diabetes, multiple sclerosis, stroke, drug side effects
(anticholinergics, antidepressants)
- Prostate: benign prostatic hypertrophy, carcinoma, infection
- Urethra: posterior urethral valves, strictures, trauma, infection, tuberculosis, tumor

Postrenal Causes of extrinsic upper - Retroperitoneal space tumors, pelvic or intra-abdominal tumors, retroperitoneal fibrosis,
urinary tract ureter ligation or surgical trauma, granulomatous disease, hematoma

Causes of extrinsic upper Nephrolithiasis, strictures, edema, debris, blood clot, sloughed papillae, fungal ball, malignancy
urinary tract
SHOCK
DEFINITION

Shock is a clinical condition of organ dysfunction caused by an imbalance between cellular oxygen
supply and demand. If left untreated, shock transitions from a reversible phase to an irreversible phase,
leading to death due to multi-system organ dysfunction.

The classification of shock is divided into 4 major categories:

Pathophysiology of AKI due to shock
► DISTRIBUTIVE SHOCK

Distributive shock or vasodilation shock

one of the four broad classifications of disorders that lead to inadequate tissue perfusion.

Systemic vasodilation

reduced blood flow to the brain, heart, and kidneys

damage to vital organs

► NEUROGENIC SHOCK

Blood pressure instability, heart

Severe hypotension and shock
rate, and temperature regulation.

Severe brain and spinal cord injury Distributive shock in spinal cord
due to trauma injuries

Decreased blood vessel resistance

Autonomic pathway disorders
and changes in vagal tone
 The mean arterial Activation of the Release of renin and
pressure decreases sympathetic nervous system antidiuretic hormones.

Constriction of arterioles and venules as Occurs primarily in the renal, splanchnic,

well as stimulation of cardiac function and musculocutaneous circulations.

Maintains blood flow to the Reduced renal blood

heart and brain. flow and GFR ACUTE KIDNEY INJURY
► ANAPHYLACTIC SHOCK

Anaphylaxis
A severe allergic reaction that can lead to shock

Mediated by immunoglobulin E (IgE)

Acute systemic reaction  direct release of mediators from mast cells and basophils due to triggers

Examples of triggers:

Insect stings, food, and medications Exercise, contrast media, natural rubber latex, and idiopathic causes
Histamine Increases blood vessel permeability and vasodilation Tissue hypoperfusion

Prostaglandin D Bronchoconstrictor and increases blood vessel permeability

TNF-alfa Activates neutrophils and increases chemokine synthesis.

Anaphylaxis process  distributive shock and RENAL VASOCONSTRICTION

► SYOK SEPSIS

(example, Pneumococcus,
Gram-Positive Organisms Enterococcus)

Pathogen Types (example, Pseudomonas,

Gram-Negative Organisms
Causing Sepsis Klebsiella, Enterobacter)

Fungal Organisms (example, Candida)

Pathophysiological Mechanisms of Sepsis-Induced AKI

Disruption of Renal Blood Cytokine and Neutrophil

RENAL INJURY
Flow Activation

Prerenal Factors (Reduced Renal

Hypotension
Perfusion, Hypotension)

Decreased Global Renal Acute Tubular

Blood Flow Necrosis (ATN)
► CARDIOGENIC SHOCK

Intracardiac causes of heart Reduced cardiac Decreased cardiac output or systemic

pump failure output blood vessel resistance

Increased Release of renin Constriction of arterioles and

Decreased mean
sympathetic nervous and antidiuretic venules as well as stimulation
arterial pressure
system tone hormone of cardiac function

Arteriolar vasoconstriction in renal, splanchnic, Reduced renal blood

and musculocutaneous circulations flow and GFR AKI
► HYPOVOLEMIC SHOCK
Types of Hypovolemic
Shock Reduced intravascular Decreased mean Increased sympathetic
volume arterial pressure nervous system tone

hemorrhagic

Release of renin (formation of Constriction of arterioles and venules as

non-hemorrhagic angiotensin II) and antidiuretic hormone well as stimulation of cardiac function

Restoring systemic blood Arteriolar vasoconstriction in Relatively preserved

pressure and cardiac output renal, splanchnic, and blood flow to the
towards normal musculocutaneous circulations heart and brain

Reduced renal blood Gradual decrease

flow and GFR
Continuously
in GFR AKI
► OBSTRUCTIVE SHOCK
Causes of Obstructive Shock
PE or PH Right Ventricle
vascular or mechanical
obstruction

right ventricular failure Unable to generate sufficient

due to significant Hemodynamic
pressure to overcome high
hemodynamically collapse (PE)
pulmonary vascular resistance
relevant pulmonary
embolism (PE)

severe pulmonary Mediated by vasoactive

Mechanical Pulmonary
hypertension (PH) mediators like serotonin and
obstruction vasoconstriction
thromboxane

Severe stenosis or acute obstruction of the

Obstructive shock
pulmonary or tricuspid valve
 SUMMARY
Acute Kidney Injury (AKI), or acute renal failure, is defined by a disturbance in kidney filtration and
excretory function lasting for days to weeks, leading to the retention of nitrogen and other waste
products typically eliminated by the kidneys.

AKI is a term for a heterogeneous group of conditions that share common diagnostic features,
notably an increase in serum creatinine concentration along with a decrease in urine volume.

The etiology of AKI is divided into prerenal, intrinsic renal, and postrenal causes.
 SUMMARY
Shock is a clinical condition of organ dysfunction resulting from an imbalance between cellular oxygen
supply and demand.

Shock can transitions from a reversible phase to an irreversible phase, leading to multisystem organ
dysfunction and death.

Clinicians must promptly identify patients in shock, make an initial assessment of the type of shock
present, and initiate therapy to prevent irreversible organ dysfunction and death.

Shock is classified into four major categories: distributive shock, cardiogenic shock, hypovolemic shock,
and obstructive shock.
 SUMMARY
The cellular oxygen imbalance in shock is most often related to oxygen delivery disruption in the context
of circulatory failure.

Shock can also develop during conditions of increased oxygen consumption or impaired oxygen utilization.
The influx of calcium can trigger the activation of calcium-dependent phospholipases and proteases, leading
to swelling and cell death.

A common endpoint in all types of acute tubular necrosis is cellular damage, either due to ischemia or
direct toxins, resulting in brush border depletion and eventual cell death, which can lead to tubular cell
dysfunction and failure.
Thanks!
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