Intensive care of acute kidney and hepatic insufficiency

 

Acute renal failure

Kidneys are the pair organs located in the retroperitoneum (at

the level of 12_th rib in the loin region). Their main function is

elimination of the metabolic wastes from the organism. They are

supplied with blood by paired renal arteries, which are direct arterial

branches of abdominal aorta.

Nephron is the basic functional unit of the kidneys. Its structure

is quite complicated: it consists of renal corpuscle (Bowman_

Shumlanski’s capsule and glomerulus), proximal convoluted tubule,

loop of Henle, distal convoluted tubule and direct tubule.

Kidneys are exclusively “hard_working” organ. Their total weigh

is hardly 0,4% of the total body weight, however they receive 25 % of

cardiac output. 10% of total inhaled oxygen are used for their

metabolic needs. During the day nearly 150 liters of primary urine

are ultrafiltrated out of the blood. Ultrafiltration is possible only

when effective filtration pressure is not less than 12 mm Hg. It is

defined as a difference between hydrostatic (47 mm Hg), oncotic

(25 mm Hg) and intracapsular pressure (10 mm Hg).

EFP=Hp(47)_Op(25)_ICp(10)= 12 mm Hg

So when hydrostatic pressure (mean arterial pressure) is

decreasing or when intracapsular pressure is reaching critical values

filtration stops and renal failure appears.

In tubules water, electrolytes and glucose are reabsorbed and

metabolic wastes are secreted to the urine. Eventually during one

day only 1 % of primary urine is evacuated from the organism in the

form of secondary urine with high concentration of toxic substances.

Kidneys participate in haematopoiesis, regulation of fluid

balance, electrolytes metabolism and acid_base balance.

Kidneys are also organs of secretion: their parenchyma produces

rennin – substance very important for vascular tone regulation.

Etiology and pathogenesis of acute renal failure

(acute kidneys injury)

Acute kidneys injury is a syndrome appearing due to sudden and

progressive affection of nephrones, which causes violation of renal

function and induces life_threatening homoeostasis disorders.

The reasons of acute kidney injury are divided into 3 gorups:

1. Prerenal: pathological conditions, which lower renal blood flow,

such as hypovolemia, hypotension, thrombosis, renal artery embolism,

renal artery spasm, haemolysis, myolysis (muscle desintegration). Thus

the prerenal failure can be connected with the massive blood loss, shock

(traumatic, anaphylactic, cardiac), dehydration (burns, pancreatitis,

peritonitis, vomiting, diarrhoea), crush_syndrome, transfusion of

incompatible blood, acute respiratory failure.

2. Intrinsic: the primary damage is caused to the renal

parenchyma by exogenous toxins (alcohol surrogates, acetic acid,

ethylene glycol, heavy metal salts), nephrotoxic antibiotics

(aminoglycosides), bacterial toxins (in case of sepsis), acute

glomerulonephritis, eclampsia.

3. Postrenal: acute renal failure appears due to complications of

urine outflow (tumours and calculi of renal pelvis and ureter, prostate,

accidental ligation of the ureters during operation).

In 70% of the cases acute renal injury appears as a result of

prerenal cause. In stress conditions (massive blood loss, multiple

injuries) adrenals intensively produce catecholamines: arterioles of

skin, smooth muscles, intestines and kidneys spasm. As you probably

remember this helps to save the brain and heart (additional blood for

circulating blood volume), however for the rest organs this situation,

lasting over 3_4 hours means ischemia and even necrosis.

Another mechanism for acute renal failure is connected with the

acute vascular insufficiency (collapse, endotoxicosis). Hydrostatic

pressure decreases and thus filtration of the blood lowers.

The mechanism of this pathological process is next:

hypoperfusion_renal ischemia_hypoxia_coagulation of blood in

glomerular vessels_termination of plasma filtration_affection of

tubules membranes– compression of the nephrons and capillaries_

renal necrosis.

Death of over 75% of nephrons finds its clinical manifestation in

acute kidneys injury. All the functions of the kidneys– ultrafiltration,

reabsorption, secretion, bioactive substances production – are

violated.

 Stages of acute kidneys injury: clinic and

treatment

Clinically in case of acute kidneys injury we differentiate 5 stages:

I. First stage (initial) is the stage of shock: depends on the initial

aggressive agent and duration of its influence. It can last several hours

or several days (2_3). Clinic also depends on the causing factor,

however first of all you should observe carefully the haemodynamics

and urine output, because correct evaluation of patient’s condition

and proper treatment may prevent the development of next stages.

Warring symptoms are:

arterial hypotension (systolic blood pressure less than 70 mm

Hg if it remains during few hours);

decrease of urine output;

hyposthenuria (low specific gravity– less than 1006_1008)

Intensive treatment depends on the primary disease. So you have

next possibilities:

1. Hypovolemic shock: profuse bleeding, plasma loss,

dehydration.

a. restore the circulating blood volume (blood components

transfusions, colloids and crystalloids infusions, glucose solutions) –

on time provided correction of circulating blood volume (and you

will notice it through normalization of blood pressure, pulse,

haemoconcentration indexes and especially central venous

pressure) – in most cases means restore of the diuresis.

b. if there is no effect of infusion therapy: liquidate renal arteries

spasm and restore microcirculation _ give β_adrenoceptor antagonists

(droperydol, aminazin, ganglionic blockers, epidural anesthetics);

stimulate diuresis with 30% mannitol solution 1 g/kg i/v with the

speed 80_100 drops per minute (with 40% glucose solution), 1%

furosemid solution (beginning with 2_4 ml every 7_10 minutes and

up to 40_50 ml); use additionally spasmolytics (10 ml of 2% euphillin

solution i/v with saline). This “triple shot” combined with infusions

can liquidate the functional renal failure.

2. Acute vascular insufficiency: anaphylaxis, toxic collapse,

orthostatic collapse caused by overdose of ganglionic agents or

β_adrenoceptor antagonists; “warm phase” of bacterial shock;

reflectory cardiogenic shock.

a. stabilize vascular tone and perfusion pressure with

adrenomimetics (epinephrine, dopamine, mezaton i/v, best of all with

infusion pump).

b. use steroids, colloids and crystalloids, steroids and then –

stimulate the diuresis (described above).

3. Hemolysis (reactions after blood transfusions, hemolytic

poisonings, true drowning in sweet water, some snakebites and insect

bites, myolisis during crash_syndrome):

a. increase the circulating blood volume providing hemodilution

through infusion therapy;

b. increase blood pH infusing 4% solution of sodium bicarbonate

(however don’t forget to control its level);

c. liquidate spasm of renal arteries;

d. stimulate diuresis.

In case of intense hemolysis, injuries with massive muscle

disintegration it would be wise to begin preventive hemodyalisis.

4. Renal diseases: normalize hemodynamic indexes, give

spasmolytics, stimulate diuresis and use antihypoxic treatment.

5. Postrenal reasons of acute kidneys injury demands immediate

consultation of urologist and decision about operative liquidation of

urine flow obstruction (insertion of catheters into the bladder, ureters;

epicystostomy, prostatectomy, lithotomy, etc.). Do not stimulate urine

output with diuretics until the reason of obturation is not removed!!!

Lack of diuretic effects after stimulation states severe organic

injury of nephrons and you should make a diagnosis of acute renal

failure, stage of oligoanuria.

II. Second stage– oligoanuria– lasts from several days to 3 weeks

(duration depends on the degree of the damage and regeneration

ability of the nephrons). It can manifest as oliguria (urine output less

than 500 ml/day) or anuria (urine output less than 50 ml/day).

The severity of this stage is determined with its symptoms:

1. Overhydration: quite often it is caused by iatrogenic reasons –

doctors try to “overfill” patient with the water to stimulate diuresis

(outdated and dangerous conception!) or simply calculate the daily

fluid balance in a wrong way (too “positive” balance).In addition this

phase is characterized by intensive catabolism (tissues destruction)

and thus excessive endogenous water production (up to 1500 ml/

day). Clinical findings: increase of the body weight, circulating blood

volume, blood pressure, central venous pressure, peripheral oedema,

possibly pulmonary oedema.

2. Electrolytic disorders: hyperkalemia, hypermagnesemia,

hypocalcemia. Clinical findings: depression, somnolence, hyporeflexia,

respiratory and cardiac disorders.

3. Metabolic acidosis is caused by accumulation of hydrogen ions

due to disorders of their renal secretion. Clinical findings: noisy rapid

deep breathing (compensatory Kussmaul breathing), vomiting,

evident haemodynamic disorders.

4. Uraemic intoxication. Clinical findings: consciousness

disorders (up to coma), ammonia breath odour, uraemic polyserositis

(pleuritis, pericarditis), ulceration of oesophageal mucous membrane

and gastric mucous membrane, diarrhoea.

5. Disorders of synthetic renal function. Clinical findings: anaemia

due to erythropoietin deficiency and hypertension (connected with

renin_angiotensin disorders).

Intensive treatment.

Your therapeutic tactic will differ a lot in comparing with the

previous phase.

1. Fight with overhydration. First of all medical stuff should

control carefully body weight gain: ideally correct treatment excludes

increase of the weight. Everyday patient loses 400_500 ml of water

with respiration. Don’t forget to count water loss with vomiting and

diarrhea. Infusion therapy should not exceed this total fluid loss and

the only solutions you should use are normal saline and 20_40%

glucose solutions (with insulin).

2. Control and treat electrolyte disorders: prescribe calcium

chloride or calcium gluconate solutions (40_50 ml of 10% solution

intravenously). Calcium acts as potassium and magnesium antagonist

and thus lowers their plasma concentrations.

3. Treat metabolic acidosis with 4% sodium bicarbonate solution

(up to 400_500 ml per day with acid_base control tests). Normalization

of blood pH also normalizes potassium level.

4. Catabolism inhibition: to prevent tissues destruction use

anabolic hormones (Nerobol, Retabolil) which prevent muscle

disintegration and breakdown of the proteins. This helps to reduce

endogenous water production and toxins production. For this

purpose we are also using concentrated glucose solutions.

5. To eliminate the wastes from the body there are different

methods: enterosorbtion (enterodez, polisorb, activated charcoal,

etc.), intestinal lavage (cleansing enemas 4_6 times a day),

extracorporeal detoxification methods (hemodyalisis,

plasmapheresis, hemosorbtion), peritoneal dialysis.

6. Symptomatic treatment: prescribe hypotensive medicines if

necessary, preparations for cardiac support, transfuse washed red

blood cells. Prevent infectious complications.

Don’t forget, that in case of acute kidneys injury withdrawal of

many drugs is delayed or interrupted and thus accumulation effects

are possible!

Hemodialysis is the process of extracorporeal waste products

removal with the help of “artificial kidney”. The principle of its work is

quite simple: special pump pushes the blood through the tubes to the

dialyzer. Dialyzer itself is a system of capillaries, made of semipermeable

membrane (kuprofan, cellophane), which are “immersed” into the

dializing solution (something chemically very close to plasma). When

blood passes through the capillaries dialysis, osmosis and ultrafiltration

take place. During this process toxic wastes (creatinine, urea, uric acid,

phosphates, potassium and hydrogen ions) and excessive water move

to the dializing solution. Simultaneously ions of sodium and calcium

move from the dializing solution into the blood.

According to the method of blood taking and blood return

dialysis is conducted through arterial_venous access or venous_

venous access. Aseptic conditions are obligatory; anticoagulants are

used in most cases (heparin solution). Average blood speed of 200_

250 ml/minute determines duration of dialysis up to 4_5 hours.

Absolute indications to haemodialysis are:

overhydration (CVP over 15 cm H2O);

hyperkalaemia (potassium more than 7 mmol/l);

creatinine more than 0,3 mmol/l;

decompensated metabolic acidosis (pH<7,2);

daily growth of urea > 5 mmol/l, urea level over 35 mmol/l.

Contraindications to haemodialysis:

unstable haemodynamics (blood pressure less than 90 mm Hg);

haemorrhagic syndrome;

decompensated cardiac and respiratory insufficiencies;

– CNS damages (stroke, intracranial haematoma).

III. Third stage is a stage of diuretic function restoring. It begins

when the daily urine output becomes more than 500 ml and lasts

for 3_5 days. Due to regeneration of the glomeruli blood filtration

is gradually restored. Tubules epithelium regenerates a bit slower

and thus water reabsorption is still inadequate. Diuresis growth

every day and at the end of this phase reaches 1500_2000 ml per

day. However urine has low specific gravity and contains large

amount of red blood cells and protein. Hyperkalaemia and uraemic

intoxication are still dangerous, because wastes elimination is not

adequate.

So the intensive treatment is quite similar to the previous stage.

You can change the volume of infusions (but again – control the

daily balance of fluid). When daily urine output will reach physiologic

point of 2_3 liters next stage starts.

IV. Forth stage is a diuretic stage (polyuria). It lasts up to 2

weeks. Daily diuresis increase is 800_1000 ml and daily urine output

reaches 7_9 liters. Biochemical blood tests get to the norm (urea,

creatinine). Due to excessive diuresis dehydration and electrolyte

imbalance develop: potassium and magnesium ions are lost in large

amounts and this can bring life_threatening complications.

Intensive treatment hass changed: now your task is to restore

the circulating blood volume and lost electrolytes reserves.

Correction is made according to the laboratory tests and special

formulas.

Gradually concentrating ability of kidneys is returned and

diuresis is normalized (specific gravity gets to norm, electrolytes are

reabsorbed).

V. The fifth stage is a stage of recovery. It takes few months or

few years to gain complete recovery and for some patients everything

will end with a chronic renal failure. In this stage your task is to

prescribe symptomatic treatment, proper diet and resort therapy.

 

Acute liver failure

Liver is the largest internal organ, unpaired triangular gland

located in the right upper quadrant of the abdominal cavity, below

the diaphragm. It is extremely important for the organism because

of the variety of activities it performs. Liver is a digestive gland

(produces and excretes bile necessary for lipids consumption), a

detoxification centre (microsomal oxidation allows detoxification

of exogenous and endogenous toxic substances) and a synthetic

center, where proteins, lipids and carbohydrates are metabolized.

Liver is also an organ of haematopoiesis and a blood reservoir.

Additionally it helps to control acid_base balance.

To provide its metabolic needs with the oxygen organism gives

nearly 25% of total consumed oxygen; in case of severe intoxication

this number growth up to 40% of the total oxygen. Blood flow of the

liver is for 20% provided by hepatic arteries and for 80% by the portal

vein. Thus the blood liver receives is poorly oxygenated and any

hypoxic condition will bring oxygenation disorders first of all to the

tissues of the liver. This evolutionary resulted in unique regeneration

abilities of the liver: death of 70% of cells will end up with a failure;

however after a certain adaptation period hepatic tissues will restore

their quantity and quality.

7.2. Acute liver failure: etiology and pathogenesis

Acute liver failure is a state of hepatic cells dysfunction, caused

by unknown earlier liver disease, resulting in general intoxication,

coagulation violations, neurological and mental disorders. Its

etiology is usually connected with: viral hepatitis (hepatitis B virus,

hepatitis A virus), poisonings (mushrooms, dichlorethane,

phosphorus, carbon tetrachloride, arsenic), eclampsia, burn disease,

anaesthetic gas, antibiotics, sulfanilamides, massive bacterial

pneumonia, cirrhosis, hepatic tumours and metastases.

Advanced liver failure manifests in coma. Hepatic coma is divided

into endogenous (“destructive”, hepatocellular) and exogenous

(“shunt”, porto_caval). Toxic damage of 70% of liver cells will cause

endogenous coma. In case of liver cirrhosis high portal pressure

antagonizes portal blood flow and thus most of the blood moves to

the caval venous system and is not detoxified – exogenous coma

appears. Clinically we usually observe mixed comas.

Central nervous system in case of liver failure is affected in various

ways. Ammonia encephalopathy appears because of violations of uric acid

synthesis (it is made from ammonia and without this process ammonia

concentration increases several times). Food reach with proteins stimulates

ammonia encephalopathy onset, as well as gastrointestinal bleedings,

hypnotic medicines and opiates, alcohol, surgeries, infections and metabolic

alkalosis. In the CNS tissues false mediators like octopamine, amino acids

and their toxic metabolites are accumulated. On the background of

hypoproteinemia interstitial edema appears and this brings respiratory

hypoxia of tissues. At the same time violated synthesis of enzymes,

disordered metabolism of carbohydrates and lipids, metabolic alkalosis

with hypokalaemia just advance the encephalopathy.

 Clinical findings in case of liver failure

Liver failure has several forms:

1. Excretory form (disorders are mostly connected with bile

production, jaundice is the main characteristic).

2. Vascular form (clinically portal hypertension is the most noticeable).

3. Hepatocellular form (most clinical sings are caused by disorders

of synthetic metabolism in liver cells).

According to the duration of the process we define acute and

chronic liver failure, according to the compensation level–

compensated, subcompensated and decompensated failure.

Central nervous system is damaged gradually: it begins with

precoma and progresses into moderate and deep coma.

Clinical findings:

skin: jaundice, vascular spiders, “hepatic” palm, extension of

small superficial face vessels;

fever;

hepatic breath odour, hepatic smell of sweat and urine (this

smell occurs due to transformation of methionine into methyl

mercaptan);

digestion disorders (nausea, hiccups, inappetence, smooth red

tongue, abdominal pain, meteorism, defecation disorders);

obstructive and diffuse respiration disorders – hypoxic

hypoxia;

cardiovascular disorders (arterial hypotension, tachycardia,

extrasystoles);

haemorrhagic syndrome, anemia (due to interruption of

coagulation factors synthesis and bleeding of gastric or oesophageal

erosions and ulcers);

frequent additional complications: renal failure, hepatorenal

syndrome (prognostically very dangerous).

If liver failure progresses CNS damage deepens and you can

clinically observe: weakness, headache, sluggishness, apathy, inversion

of sleep and awakening. Disorientation develops gradually, there is

possibility of excitement periods and cramps. You can also find

overactive tendon reflexes, foot clonus, Babinski’s sign. One of the most

significant symptoms is flapping: trepidation of limbs and face, especially

of hands in prone position (arms extended). In case of deepest coma you

will see dilated pupils, eyeballs are fixed, tendon reflexes are absent.

Progressive and quick decrease of liver size is a prognostically

bad sign. However when the disease is chronic and fibrous changes

took place this symptom is not noticed (liver stays enlarged).

 Intensive treatment

The basic principle of liver failure treatment is etiologically aimed

therapy: you should treat the reason of the failure. Two other important

components are prevention and treatment of liver failure complications

during 10_14 days necessary for the regeneration of the hepatocytes.

Necessary treatment measures:

1. Patient should follow strictly bed regiment in isolated ward.

Medical stuff should follow asepsis and antisepsis rules.

2. Eliminate animal fats and proteins from the patient’s diet to

prevent encephalopathy.

3. Liquidate hepatotoxic factors (hypoxia, hypovolemia,

haemorrhagic syndrome, intoxication):

– provide oxygen supply (nasal catheter, face mask with the flow

3_4 l/min); sometimes hyperbaric oxygenation and even intestinal

oxygenation (0,2_0,3 ml/kg/min) are possible;

to increase hepatic blood flow restore the circulating blood

volume, improve rheological properties of the blood, restore the

peristalsis. To achieve this you should: infuse crystalloids and glucose

solutions, spasmolytics, 2 % euphyllin solution (20_30 ml/day). 10%

albumin solution (200_300 ml) and mannitol solution (1 g/kg)

increase oncotic blood pressure and prevent interstitial oedema of

the liver;

– prevent ulceration of stomach and gastrointestinal bleeding

by prescription of famotidine or omeprazole (40 mg twice a day);

oesophageal bleedings are stopped with Blackmore probe;

if you suspect stagnated blood in the intestines – remove it,

because otherwise intoxication will get more intense;

– use only “fresh” blood stabilized with heparin for transfusions.

Prevent and treat intoxication with:

intestinal lavage and enemas;

antibiotics which are not toxic to the liver (for example

ampicillin 1,0 every 4 hours);

extracorporeal blood detoxification (plasmapheresis,

hemosorbtion or hemodialysis; usage of artificial liver or artificial

spleen);

– prescribe antagonists of ammonium (40_50 ml of 1% glutamic

acid solution with glucose 3 times a day; 2,0 of alfa_arginine solution

i/v every 8 hours).

4. To stimulate energetic metabolism in hepatocytes prescribe

concentrated glucose solutions (10_20% solutions, up to 5g/kg/day).

This will also prevent proteins breakdown and thus wastes

accumulation.

5. To stabilize the membranes of the hepatocytes prescribe

steroids (10_15 mg/kg of hydrocortisone).

6. To stabilize the energetic exchange and stimulate

transportation of the lipids prescribe choline chloride (10 ml of 10%

solution with 200 ml of glucose solution after previous atropine

admission, twice a day).

7. Additionally prescribe vitamins (ascorbic acid, B1, B2, B6, K, E,

B12, folic and nicotinic acids in doses 2_3 times higher than daily needs),

cardiac glycosides, panangin, antioxidants (cytochrome c, sodium

gamma_hydroxybutyrate).

8. Symptomatic treatment helps to stabilize homoeostasis if not

to treat failure itself: if necessary use anticonvulsive medicines,

antipyretics, etc.