Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_2683_Библиотеки_им_академика_М_И_Перельмана.pdf
Gastrointestinal and hepatobiliary systems
• Hypoglycaemia: may occur with fulminant hepatic
failure.
• Serum alpha-fetoprotein (AFP): levels increased
transiently in patients with acute viral hepatitis.
Management—The causes range from infective (e.g.,
viral or bacterial), to drug-induced, to autoimmune, to alcohol. Management depends on the cause. Mild disease can
be managed conservatively with simple analgesia, alcohol
avoidance and good nutrition. Cholestyramine may alleviate itching. Severe disease may progress to liver failure.
Patients should be barrier nursed until the cause of hepatitis is identified. Use of all unnecessary drugs should be
stopped.
Autoimmune hepatitis
Autoimmune hepatitis is caused by autoantibodies against
hepatocytes, causing an inflammatory condition of the liver.
It predominantly affects young and middle-aged women,
and is associated with thyroiditis, diabetes mellitus, ulcerative colitis and fibrosing alveolitis. Clinical features may
be insidious, and include fever, right upper quadrant pain,
jaundice, epistaxis and gum bleeding, polyarthritis, urticaria and glomerulonephritis.
Investigations reveal deranged LFT values (raised
AST/ALT levels) and raised IgG levels. Autoantibodies
anti-liver-kidney microsomal (anti-LKM), anti-nuclear
(ANA), anti-mitochondrial (AMA) and anti-smooth muscle antibodies) may be present. Liver biopsy will show
mononuclear cell infiltration of portal and periportal regions with piecemeal necrosis, fibrosis or cirrhosis.
Treatment includes orally administered prednisolone, reduced over time and maintained for 2years. If treatment is
stopped, autoimmune hepatitis relapse is likely. Azathioprine
may need to be added. Rituximab or methotrexate can be
considered. If decompensated liver failure secondary to cirrhosis is present, liver transplantation is indicated.
Alcoholic liver disease
Men who drink more than 50 units and women who drink
more than 35 units of alcohol per week have a significant risk
of developing cirrhosis. Ten percent to 20% of people with
chronic alcoholism develop cirrhosis. Risk factors include
genetics, female sex (women develop alcoholic hepatitis and
cirrhosis younger, and after less intake, than men), poor nutrition (alcohol is better tolerated under optimal dietary conditions) and a synergistic effect with hepatotrophic viruses.
Pathology
Initially there are fatty changes within the liver. With alcoholic hepatitis, there is liver cell necrosis and generalized
inflammation. Cells contain alcoholic hyaline or Mallory
bodies. Later there is deposition of collagen around the central veins, which may spread to the portal tracts.
Cirrhosis may result, which is initially micronodular. Extensive fibrosis contributes to the development of
portal hypertension. With continued cell necrosis and
regeneration, the cirrhosis may progress to a macronodular pattern.
Clinical features
The patient may initially be asymptomatic. With alcoholic hepatitis, there may be fatigue, anorexia, nausea and
weight loss. There may be signs of chronic liver disease (see
Chapter14).
Hepatic decompensation leads to encephalopathy and
liver failure. Precipitating factors are listed in Table29.7.
With advanced cirrhosis, there may be signs of malnutrition, ascites, encephalopathy and a tendency to bleed
(thrombocytopenia and coagulopathy). Signs include bilateral parotid enlargement, palmar erythema, Dupuytren
contractures and multiple spider naevi. Men develop gynaecomastia and testicular atrophy. Portal hypertension develops, leading to splenomegaly and distended abdominal
wall veins. Oesophageal varices are often present. There
may be signs of alcohol damage in other organs (e.g., peripheral neuropathy, cardiomyopathy, proximal myopathy
or pancreatitis).
Investigations
Mean corpuscular volume and γ-glutamyltransferase level
are sensitive indices of alcohol ingestion. Important variables for predicting outcome include indicators of synthetic
liver function: clotting, glycaemic control, albumin level
and LFT values.
Ultrasound examination will demonstrate fatty liver, and
histology of liver biopsy specimens will show the pathological changes discussed earlier. Transient elastography (a type
of ultrasound examination used to quantify liver fibrosis
and steatosis) can be used to diagnose cirrhosis. Patients
with an established diagnosis of alcohol-related liver disease
should be offered 2-yearly cirrhosis retesting.
Management
Patients should be counselled to completely abstain from alcohol. General measures for the management of chronic liver
disease should be instigated. Patients may need nutritional
support, including vitamins B and C. Liver transplantation
is usually offered only to fully medically managed otherwise
suitable candidates with persistent decompensated liver disease after abstinence from alcohol for at least 3months.
Prognosis
If the patient abstains from alcohol, fatty liver alone carries a good prognosis. If the patient is encephalopathic and
malnourished, mortality is up to 50%. Ascites, peripheral
oedema, persistent jaundice, uraemia and the presence of
collateral circulation are unfavourable prognostic signs.
The Child–Pugh classification (Table 29.10) is a scor-
ing system that was originally used to estimate the risk of
complications, especially in cirrhotic patients considered
for liver transplantation; however, it has now been largely
replaced by the newer Model for End-Stage Liver Disease
score (clinical notes: MELD score).
248
Hepatobiliary system
Table29.10 Child–Pugh score
Points
Criteria
Encephalopathy Absent Grade 1 or 2 Grade 3 or 4
Ascites Absent Mild to moderate Severe
Bilirubin (mg/dL) <2 2–3 >3
Albumin (g/dL) >3.5 2.8–3.5 <2.8
Prothrombin time (s)
or INR
Five or 6 points corresponds to class A (low operative mortality), 7–9 points corresponds to class B (moderate operative mortality) and
10–15 points corresponds to class C (high operative mortality).
INR, International normalized ratio.
1 2 3
<4
<1.7
4–6
1.7–2.3
>6
>2.3
2929
CLINICAL NOTES
MELD SCORE
The Model for End-Stage Liver Disease score
is used to evaluate liver disease severity and
predict survival. It is often used to help determine
if a patient could be considered for liver
transplantation. It is calculated by the entering
of the levels of bilirubin and creatinine and the
international normalized ratio into a mathematical
formula. The equation is adjusted if the patient has
been receiving renal replacement therapy. A score
of more than 40 corresponds to 3-month mortality
of more than 70%.
Nonalcoholic steatohepatitis
Nonalcoholic steatohepatitis (NASH) is an increasingly
common condition because of the obesity epidemic. The
condition is characterized by fatty deposit in the liver in
association with inflammation. NASH without inflammation is termed ‘nonalcoholic fatty liver disease’. It is
typically asymptomatic, but occasionally a smooth hepatomegaly may be felt on examination. The diagnosis
may be suspected because of chronically elevated aminotransferase levels, typically with an AST-to-ALT ratio less
than 1. Alkaline phosphatase and γ-glutamyltransferase
levels are usually raised. Liver ultrasound scan will show
diffuse hyperechogenicity. Treatment is predominantly
lifestyle-based: increased exercise and weight loss have
been shown to reverse early disease. Tight glycaemic
control is important as diabetic patients are at increased
risk of NASH. NICE guidelines developed in 2016 advise
that pioglitazone or vitamin E should be considered when
advanced fibrosis is present. Prognosis is good if lifestyle
changes are made, but NASH can progress to cirrhosis and
hepatocellular carcinoma.
Haemochromatosis
Haemochromatosis is due to excess iron in the tissues. The
presence of skin discoloration and diabetes mellitus led to it
being called ‘bronze diabetes’ in the past.
Haemochromatosis may be classified as hereditary (‘primary’) or secondary. Hereditary haemochromatosis is autosomal recessive. Secondary haemochromatosis may result
from excessive iron administration (e.g., blood transfusion
or iron tablets).
Affected organs include the liver, endocrine system,
heart and joints. Most patients are asymptomatic or have
nonspecific symptoms such as arthralgia and lethargy, until the effect of iron overload becomes apparent in the fifth
or sixth decade. Joints are involved by chondrocalcinosis,
which is associated with synovial haemosiderin and loss of
intraarticular space.
In the early stages, pain and swelling of the second and
third metacarpophalangeal joints is characteristic. There
is slate-grey skin, due to melanin, and iron deposition.
Symptoms include asthenia, abdominal pain, impotence,
arthralgia and amenorrhoea. Signs include hepatomegaly,
splenomegaly, jaundice and gynaecomastia. The disease
may lead to cirrhosis.
The prevalence ranges from 1 in 200 to 1 in 2000,
and men are 5–10 times more likely to be affected than
women, indicating that environmental and genetic factors modify disease expression. Alcohol may exacerbate the disease by influencing iron absorption and
metabolism.
Total body iron is increased in haemochromatosis from
4 g to as much as 60 g. There is cellular damage and fibrosis,
leading to a rusty colour of the liver, pancreas, spleen and
abdominal lymph nodes. Complications include diabetes
mellitus, cirrhosis, heart disease with arrhythmias and liver
cancer.
Investigations
• Serum ferritin level is high (however, this is of low
specificity as it can be raised in a number of other
conditions).
249
Gastrointestinal and hepatobiliary systems
• Serum iron level is elevated, and saturation of plasma
transferrin is high (however, these findings alone
should not be used for diagnosis as they do not
adequately reflect total body iron).
• Definitive diagnosis of haemochromatosis depends on
histology of liver biopsy specimens.
• CT scanning and MRI can be used to detect increased
tissue iron but are not routine.
• Genetic testing can be performed to look for the most
common mutations (C282Y and H63D).
Management
Patients should be venesected regularly (400–500 mL
weekly), until they develop a mild microcytic anaemia. Care
is needed in patients with severe hepatic disease because vigorous bleeding may be complicated by hypoproteinaemia.
Folate supplementation may be needed to optimize erythropoiesis. Seriously ill patients with overt cardiac haemochromatosis may require high-dose parenteral chelation therapy
with desferrioxamine to reverse life-threatening disease.
Patients with established haemochromatosis should be
investigated for cardiac involvement and pituitary, as well
as target organ endocrine failure, and replacement therapy
should be instituted when necessary. Patients should be reviewed to monitor diabetic control, to care for joint disease
and to inspect them for the development of complications
(e.g., hepatocellular carcinoma).
Life expectancy and hepatic and cardiac function in primary haemochromatosis are improved by iron depletion.
The 5-year survival rate increases from 30% to 90% with
treatment. Removal of iron does not prevent the development of cancer in patients with established cirrhosis.
Primary biliary cholangitis
Primary biliary cholangitis (PBC) is an autoimmune disorder
primarily affecting the small intrahepatic bile ducts (canals of
Hering) as a nonsuppurative, destructive cholangitis leading
to bile duct damage, cholestasis, fibrosis, cirrhosis and death
from liver failure. It is more common in Europe than in Africa
and Asia. The UK prevalence is around 13 per 100,000.
Women are nine times more likely to be affected. PBC
usually presents in middle age with lethargy and pruritus.
Pigmentation and xanthomata may be present, jaundice
may develop and portal hypertension may lead to ascites
or oesophageal varices. There may be stigmata of chronic
liver disease. Approximately 25% have hepatomegaly at
presentation, and 15% have splenomegaly. The patient
may be asymptomatic at presentation, or may present with
liver failure. Investigations will show deranged LFT values (obstructive pattern with raised alkaline phosphatase,
γ-glutamyltransferase and bilirubin levels in late disease).
Immunologically, HLA-B8 and HLA-DR3 are associated
with a threefold increase in the risk of primary biliary cholangitis. Serum immunoglobulin levels are raised, especially
IgM level. There is antimitochondrial antibody positivity in
90%–95% of cases.
Ultrasound examination of the liver is important to exclude obstruction. It can also show evidence of portal hypertension and splenomegaly. Histology of the liver will
confirm the diagnosis. Initially, there is asymmetrical destruction of bile ducts and surrounding lymphocytic infiltrate. Granulomas may be present. Increasing fibrosis, and
eventually cirrhosis, develops.
The average life expectancy is 10 years from diagnosis but differs considerably. If the serum bilirubin level is
greater than 180 μmol/L, the life expectancy is 18months
without transplantation.
PBC is associated with autoimmune conditions (e.g.,
Sjögren syndrome, thyroid disease, Addison disease, Raynaud
syndrome, systemic sclerosis and coeliac disease). It is also associated with malabsorption, extrahepatic malignancies, particularly of the breast, and hepatocellular carcinoma. Around
50% of people with PBC develop renal tubular acidosis.
There is no evidence of benefit from the use of immunosuppressive agents. Bile salts (e.g., ursodeoxycholic acid) may
help with cholestasis, and improve biochemical blood results,
and slow progression in early disease. Liver transplantation is
indicated for intractable symptoms or end-stage disease.
Patients with jaundice should receive supplementation
with fat-soluble vitamins A, D and K. Diarrhoea is treated
with a low-fat diet and pancreatic supplements.
Primary sclerosing cholangitis
Primary sclerosing cholangitis is characterized by inflammation, scarring and narrowing of the intrahepatic and
extrahepatic bile ducts. The cause is unknown, but the
condition is associated with ulcerative colitis, rarely Crohn
disease, and HIV infection. Immunologically, there is an
association with HLA-A1, HLA-B8 and HLA-DR3. The
clinical features are due to chronic biliary obstruction, and
include jaundice, hepatomegaly, pruritus, fatigue and abdominal pain. Patients are at increased risk of ascending
cholangitis, cholangiocarcinoma and autoimmune hepatitis.
Blood tests reveal elevated alkaline phosphatase or
γ-glutamyltransferase and bilirubin levels. Tests for antinuclear antibodies, perinuclear antineutrophil cytoplasmic
antibodies, and anticardiolipin antibodies may be positive.
MRCP is the imaging method of choice, and shows multiple
bile duct strictures with a characteristic beaded appearance.
ERCP allows stricture dilation and stenting. Liver biopsy
shows fibrous, obliterative cholangitis.
Management is symptomatic. Ursodeoxycholic acid is
used to relieve cholestasis. Liver transplantation is indicated
for end-stage disease
Wilson disease (hepatocellular degeneration)
Clinical features
This is an autosomal recessive disorder (gene on chromosome 13) of copper metabolism leading to deposition of
copper in:
250
Hepatobiliary system
2929
• liver: cirrhosis with its ensuing complications;
• basal ganglia: tremor and choreoathetosis;
• cerebrum: dementia and fits;
• eyes: Kayser–Fleischer rings (a brown pigmentation
of the periphery of the iris best seen with a slit
lamp);
• renal tubules: renal tubular acidosis;
• bones: osteoporosis and osteoarthritis;
• red blood cells: haemolytic anaemia.
Clinical features are usually due to hepatic or central nervous system involvement.
Investigations
There is a high concentration of copper in the blood, and
a low concentration of caeruloplasmin, a copper-binding
protein.
Management
The dietary intake of copper should be reduced, and penicillamine should be given to aid the elimination of copper
ions. Regular blood counts are mandatory because of potential agranulocytosis and thrombocytopenia with treatment.
Other side effects include oedema, proteinuria, haematuria,
rashes, loss of taste and muscle weakness. Relatives should
be screened. The prognosis is generally good.
Hepatic tumours
Benign tumours
Benign tumours of the liver are often an incidental finding
on CT or ultrasound scan. Haemangiomas are the most
common. Cysts, adenomas, fibromata, focal nodular hyperplasia and leiomyomas are further types of benign liver
tumours. Haemangiomas should not be biopsied because
of bleeding risk. Unless they are symptomatic, tumours are
managed conservatively.
Malignant tumours
The most common malignant liver tumours are metastases. Primary tumours that tend to metastasize to the liver
include colon, stomach, lung, uterus, breast, pancreas and
carcinoid tumours. Lymphoma and leukaemia may also
spread to the liver. Primary carcinomas of the liver are less
common, although they are increasing in incidence, and
include hepatocellular carcinoma (HCC), angiosarcoma,
cholangiocarcinoma and fibrosarcoma. HCC is by far the
most common primary liver tumour and is associated with
viral hepatitis, cirrhosis (and therefore alcohol excess), parasite infection and anabolic steroid use. Clinical features
of malignant liver cancer, primary or secondary, include
weight loss, anorexia, malaise and right upper quadrant
pain. The pain is capsular in nature and is clinically difficult
to treat. Jaundice is a late feature, if at all, except in the case
of cholangiocarcinoma. Investigations include FBC and
blood film, LFTs, hepatitis serology, AFP measurements
(AFP level is elevated in 75% of patients with HCC) and
CT or MRI scanning. Liver biopsy allows tissue diagnosis.
Treatment and prognosis in metastatic liver cancer depends on the cause and the extent of the disease. Treatment
of HCC is surgical resection if the tumour is solitary and
smaller than 3 cm or liver transplantation. Percutaneous
ablation, chemotherapy and tumour immobilization are
also used.
Miscellaneous conditions
α1-Antitrypsin deficiency
α1-Antitrypsin (A1AT) is a serine protease inhibitor, syn-
thesized in the liver, important in the correct functioning
of the inflammatory cascade. A1AT deficiency is an autosomal recessive disorder (chromosome 14), and causes
emphysema, cirrhosis and potentially hepatocellular carcinoma. The diagnosis is made by measurement of protease
inhibitor concentrations and can be screened for prenatally
with oligonucleotides. There is no cure, and management
is symptomatic. Pneumococcal and flu vaccination should
be offered. Liver transplantation is performed for end-stage
liver failure.
Liver abscess
Liver abscesses are relatively rare in the United Kingdom
but are common in the developing world. The infectious
organism can be bacterial, parasitic, protozoal or helminthic. Entry to the liver can be direct (penetrating injury),
through the portal circulation, through the systemic circulation or by ascending the biliary tree. The clinical feature
is predominantly swinging pyrexia and night sweats with
right upper quadrant pain. Tender hepatomegaly is often
present, and if subacute, it can be associated with cachexia.
A blood test may show raised levels of inflammatory markers and deranged LFT values. Blood cultures are positive
in 50% of cases, and may yield the causative organism.
Liver ultrasound examination will show defined areas of
hypoechogenicity. CT is an alternative/additional imaging
modality. Treatment can be conservative with antibiotics
or specific agents against the suspected or proven microorganism. CT- or ultrasound-guided drainage is an alternative option.
Budd–Chiari syndrome
This condition is characterized by hepatic vein obstruction,
through either thrombosis or compression, causing hepatomegaly, ascites and abdominal pain. It has multiple causes,
including hypercoagulability states, myeloproliferative disorders, hepatocellular tumours and radiotherapy, although
30% of cases are idiopathic. The investigations of choice are
ultrasound examination with Doppler or CT scans to show
hepatic vein thrombosis and ascites. Management involves
treating the underlying cause and draining the ascites.
Angioplasty or a surgical shunt may be required to bypass
the obstruction. Anticoagulation is indicated in the absence
of varices. In fulminant liver failure, transplantation should
be considered.
251
Gastrointestinal and hepatobiliary systems
Chapter Summary
• Barrett oesophagus increases the risk of oesophageal adenocarcinoma.
• Helicobacter pylori infection and chronic nonsteroidal antiinflammatory drug use are the
biggest causes of peptic ulcer disease.
• Acute gastrointestinal bleeding is a medical emergency. If severe,
oesophagogastroduodenoscopy should be performed urgently. If the cause is known to
be oesophageal varices, terlipressin should be used.
• Gastric cancer is treated surgically, and chemotherapy is not used with curative intent.
• Prolamins are food proteins responsible for immune-mediated cell damage in coeliac
disease.
• Colorectal cancer is the third commonest cancer in the United Kingdom. A national
screening program for colorectal cancer is available in the United Kingdom.
• Diverticulitis can lead to serious complications such as perforation and peritonitis.
• Clostridium difficile infection is most commonly associated with the use of
cephalosporins, β-lactam inhibitors, clindamycin, macrolides and fluoroquinolones.
• Ulcerative colitis and Crohn disease are debilitating conditions associated with serious
complications. Colon cancer surveillance is an important part of management.
• Charcot triad is typical for acute cholangitis, and includes right upper quadrant pain,
jaundice and pyrexia.
• Murphy sign is positive in cholecystitis.
• Alcohol abuse is the leading cause of liver disease.
• Acute pancreatitis is a well-known cause of acute respiratory distress syndrome. Causes
can be recalled using the mnemonic GET SMASHED.
• Alcohol is the most common cause of chronic pancreatitis.
• The 5-year survival rate in pancreatic cancer is less than 3%.
• Chronic liver disease increases the risk of developing liver cancer.
• Hepatitis B virus and hepatitis C virus lead to chronic infection and can result in cirrhosis.
• Hepatitis D virus cannot exist in the absence of hepatitis B virus.
• Nonalcoholic steatohepatitis is defined as nonalcoholic liver disease with evidence of
inflammation.
FURTHER READING
British Society of Gastroenterology: Clinical guidelines. Available
online at: http://www.bsg.org.uk/clinical/general/guidelines.
html.
NICE 2012, Dyspepsia – proven GORD. https://cks.nice.org.uk/
dyspepsia-proven-gord
NICE 2015, Dyspepsia – proven peptic ulcer. https://cks.nice.org.
uk/dyspepsia-proven-peptic-ulcer
NICE 2012 (Last updated August 2016), Acute upper gastrointesti-
nal bleeding in over 16s: management
NICE 2013, Acute upper gastrointestinal bleeding in adults. https://
www.nice.org.uk/guidance/qs38
NICE, 2014. Colorectal cancer: diagnosis and management.
NICE, 2015. Clostridium difficile infection: risk with broad-
spectrum antibiotics.
NICE, 2015. Irritable bowel syndrome in adults: diagnosis and
management.
NICE 2015, Scenario: management of non-ulcer dyspepsia: https://
cks.nice.org.uk/dyspepsia-proven-non-ulcer#!scenario
252
NICE, 2011. Colorectal cancer prevention: colonoscopic sur-
veillance in adults with ulcerative colitis, Crohn’s disease and
adenomas.
NICE, 2015. Infliximab, adalimumab and golimumab for treating
moderately to severely active ulcerative colitis after the failure of
conventional therapy.
NICE, 2013. Ulcerative colitis: management.
NICE, 2016. Crohn’s disease: management.
NICE 2015, Scenario: established Crohn’s disease: https://cks.nice.
org.uk/crohns-disease#!scenario
NICE, 2016. Non-alcoholic fatty liver disease (NAFLD): assessment
and management.
NICE, 2016. Cirrhosis in over 16s: assessment and management.
NICE, 2013. Hepatitis B (chronic): diagnosis and management.
NICE, 2013. Hepatitis B and C testing: people at risk of infection.
NICE, 2010. Peginterferon alfa and ribavirin for the treatment of
chronic hepatitis C.
NICE, 2013. Clinical guideline [CG165] Hepatitis B (chronic): di-
agnosis and management.
Renal, genitourinary and sexual
health medicine
HAEMATURIA AND PROTEINURIA
Haematuria and proteinuria are common presentations
of renal disease. They are often incidental findings on
urine dipstick testing. Isolated haematuria is covered in
Chapter15.
Proteinuria
Proteinuria is defined as an albumin-to-creatinine ratio (ACR)>2.5/3.5 mg/mmol which equates to 25–35 mg
of albumin loss per 24-hour urine collection, or a
protein-to-creatinine ratio (PCR) of more than 15 mg/
mmol, which equates to 150 mg of protein per 24-hour urine
collection. Increasingly now you will see ACR being used.
This specifically measures albumin loss, which indicates
damage to the glomerulus, and is very sensitive at detecting early-stage proteinuria (e.g. with diabetic nephropathy).
PCR measures all protein leak. It includes non-albumincontaining proteinuria, which will be present when damage
occurs at other sites of the kidney (e.g. with renal tubular
damage). PCR is more frequently used when measuring
heavy proteinuria, such with nephrotic syndrome.
Low-level proteinuria can occur in nonrenal disease,
such as urinary tract infection (UTI) and in the presence
of vaginal mucus; however, significant proteinuria—ACR
greater than 70 mg/mmol or PCR greater than 100 mg/
mmol (1 g protein leak per 24 hours)—usually indicates primary renal disease (Table30.1).
Benign proteinuria
• Functional proteinuria: pyrexia, strenuous exercise,
congestive cardiac failure, acute illnesses, pregnancy.
• Orthostatic proteinuria: common in males aged under
30years; proteinuria when upright but normal when
supine.
Pathological proteinuria
This can result from any glomerular disease associated with
damage to the basement membrane, for example:
• diabetes mellitus
• glomerulonephritis
• other causes of nephrotic syndrome (Table30.2)
Tubular or interstitial damage may cause tubular proteinuria: failure of the tubules to reabsorb some of the plasma
proteins that have been filtered by the normal glomerulus.
This protein loss is mild (i.e. ACR <70 mg/mmol or PCR
<100 mg/mmol).
30
CLINICAL NOTES
Nephrotic syndrome is the triad of proteinuria
(>3 g/day, equivalent to PCR >300 mg/mmol),
hypoalbuminaemia (<30 g/L) and oedema. It
is associated with high cholesterol level, and
individuals are at increased risk of thromboembolic
disease and infections.
Table30.1 Levels of proteinuria
Type Protein leak (g/day)
Normal 0.02
Microalbuminuria 0.03–0.3
Detectable with urinary
dipstick
Significant >1.0
Nephrotic range >3.0
Heavy >5.0
Table30.2 Causes of nephrotic syndrome
Cause Examples
Renal disease Glomerular disorders:a primary;
Systemic disease Amyloidosis
Metabolic disease Diabetes mellitus
Infection HIV infection
Malignancy Lymphoma
Drugs Gold
Familial disorders Alport syndrome
Allergy Bee stings
a
Common cause.
>0.2
secondary to a systemic disease
a
Systemic lupus erythematosus
Henoch-Schönlein purpura
a
Infective endocarditis
Malaria
Hepatitis B
Myeloma
Penicillamine
Heroin
Heavy metals
Finnish-type nephrotic syndrome
Pollen
a
253
Renal, genitourinary and sexual health medicine
Overflow proteinuria
This is when abnormal amounts of low-molecular-weight
protein (filtered at the glomerulus) are neither reabsorbed
nor catabolized completely by the renal tubular cells. There
is increased protein filtration (e.g. urinary light chains in
multiple myeloma (Bence Jones protein)).
Clinical Features
Key questions when you are taking a focused history in a
patient presenting with haematuria or proteinuria are vital
in forming your differential diagnosis:
• Has there been any visible blood (frank) or
frothy urine? The latter suggests heavy
protein leak.
• Has there been any change in urine volume?
• Are there any features of oedema, peripheral
swelling, periorbital oedema, sacral oedema or any
breathlessness? Ask about symptoms of orthopnoea
and paroxysmal dyspnoea.
• Is the patient hypertensive, is this new?
• Are there any associated systemic features
(e.g. does the patient have arthralgia or any
nasal crusting/ epistaxis which is associated
with vasculitis)?
• Are there any systemic chronic diseases?
Ask specifically about diabetes mellitus,
rheumatoid arthritis/systemic lupus erythematous
(SLE) or previous calculi and recurrent urine
infections.
• Has there been a history of acute illness, sore throat,
impetigo especially with fever (e.g. with UTI or
poststreptococcal glomerulonephritis)?
• Are there generalized features of carcinoma
(e.g. anorexia and weight loss)?
• Ask about past and current medications (e.g.
analgesics or nonsteroidal antiinflammatories
(NSAIDs)).
• Is there a family history (e.g. polycystic
kidney disease, Alport syndrome, sickle cell
disease)?
• Is there a history of significant foreign
travel (e.g. schistosomiasis or
tuberculosis)?
• Are there any risk factors for human
immunodeficiency virus (HIV) infection or
hepatitis?
Protein-to-creatinine ratio/albumin-tocreatinine ratio
This quantifies urinary protein loss. If there is a large gap
between the two readings, this suggests that there is high
loss of nonalbumin protein. This may be the case in myeloma with light chain excretion.
HINTS AND TIPS
Albumin-to-creatinine ratio (ACR) or protein-tocreatinine ratio (PCR) measurement is taken from
a spot urine sample and it correlates well with the
results from a 24-hour urine collection and is far
easier for the patient to do. Note an ACR of 70 mg/
mmol or PCR of 100 mg/mmol is equivalent to 1g of
proteinuria in 24 hours; an ACR of 250 mg/mmol or a
PCR of 300 mg/mmol is equivalent to 3 g in 24 hours.
Investigations
An algorithm for the investigation of the patient with haematuria and proteinuria is given in Fig.30.1.
Urine
• Gross appearance: visible haematuria (if painless
consider malignancy), Coca-Cola coloured urine
(think rhabdomyolysis).
• Urinary dipstick: provides initial information about
the presence or absence and degree of proteinuria and
haematuria; also test for nitrites/leucocytes/ketones/pH
and glucose.
• Microscopy and culture: infection.
CLINICAL NOTES
Urine dipsticks are very sensitive to haematuria.
Nonvisible haematuria is significant only if it is
persistent (i.e. seen on two of three dipsticks in the
absence of infection).
Blood tests
The following blood tests should be performed:
• full blood count (FBC): leukocytosis with infections,
anaemia with chronic renal failure;
• renal profile: urea, creatinine, estimated glomerular
filtration rate (eGFR), potassium and sodium;
• bone profile: calcium, phosphate, magnesium,
parathyroid hormone (PTH);
• erythrocyte sedimentation rate (ESR) and C-reactive
protein (CRP) (e.g. vasculitis);
• clotting studies: bleeding diathesis;
• blood glucose: diabetes mellitus;
• bicarbonate;
• creatine kinase: myoglobinuria;
• uric acid: gout, tumour lysis syndrome;
• blood cultures: infective endocarditis;
254
Haematuria and proteinuria
History and examination
Haematuria and proteinuria
3030
Signs or symptoms of intrinsic
renal disease
Proteinuria
Red cell casts
Abnormal creatinine
Nephrology
Urine microscopy
Quantify proteinuria
Assess GFR
Family history
Blood tests
Blood cultures
Ultrasound scan
Consider renal biopsy
Consider systemic cause
Recent urinary tract infection
NO
Urinalysis
— Dipstick
— Microscopy
— Culture
IF NORMAL
YES
Treat and review
Frank haematuria
Age >40 years
Signs or symptoms of cancer
Recurrent UTIs
UTI in males
Urology
Urine cytology
non content CT KUB
Cystoscopy ± biopsy
CT scan
MRI
PSA ± biopsy
If no cause found: follow up
and consider rare diagnosis
‘loin pain haematuria’
or factitious haematuria
Fig.30.1 Algorithm for investigation of haematuria and proteinuria. AXR, Abdominal X-ray; CT, computed tomography;
GFR, glomerular filtration rate; KUB, kidneys ureter and bladder; MRI, magnetic resonance imaging; PSA, prostate-
specific antigen; UTI, urinary tract infection.
• specialized investigations according to clinical
suspicion (e.g. serum complement, C3, C4, Antinuclear
Antibodies [ANA], antineutrophil cytoplasmic
antibodies [ANCA], antistreptococcal titres and antiGBM [glomerular basement membrane antibody]
antibodies);
• protein electrophoresis and urinary Bence Jones
protein (myeloma);
Imaging
Renal ultrasound scan is the first-line imaging study; it will
confirm whether two kidneys are present, and if there are
size or structural abnormalities. It may guide further imaging (e.g. CT; noncontrast CT is used for investigation of
renal calculi). If considering renal artery stenosis, perform
renal Doppler scans or renal magnetic resonance angiogram (MRA).
• blood film, lactate dehydrogenase [LDH], haptoglobins
and reticulocytes if haemolysis is considered (i.e.
microangiopathic haemolytic anaemia [MAHA]);
• HIV and hepatitis serology: potential causes of
nephrotic syndrome;
• cryoglobulins.
Histological diagnosis
Renal biopsy may provide the best diagnostic information
but is invasive and not without risk (1% of patients have
significant bleeding, 1 in 100 need blood transfusion and
255
Renal, genitourinary and sexual health medicine
1 in 1000 need emergency nephrectomy). Careful thought
needs to be given as to how the biopsy result will alter the
management.
CLINICAL NOTES
A renal ultrasound scan must be performed before
a renal biopsy is performed. Blood pressure control
and coagulation needs to be optimized before the
procedure.
ACUTE KIDNEY INJURY
Acute kidney injury (AKI) was previously known as ‘acute
renal failure’. AKI is a decline in glomerular filtration rate
(GFR) over hours to days. Occurrence of AKI is associated with increased morbidity, mortality and risk of developing long-standing chronic kidney disease (CKD).
Many cases can be prevented if we recognize those people
at risk of AKI. The Acute Kidney Injury Network classification is the most widely used system for staging AKI
(Table30.3)
RED FLAG
Think, is your patient at risk of injury? High-risk
groups are the elderly and those with diabetes,
hypertension, previous acute kidney injury,
existing chronic kidney disease or a single kidney.
Limit injury in this group. Pay careful attention to
hydration status, avoid nephrotoxic medications
and try to avoid iodinated contrast imaging where
possible.
CLINICAL NOTES
With acute kidney injury it is very important
to take a thorough drug history; pay attention
to drugs that interfere with renal perfusion
(e.g. NSAIDs, angiotensin-converting enzyme
inhibitors and angiotensin II receptor blockers), or
contrast medium from recent CT. Ask about new
medications (e.g. antibiotics) and any over-thecounter medications (e.g. herbal medicines).
Aetiology
It helps to think of AKI in terms of prerenal, renal and
postrenal causes (Table 30.4). Prerenal causes are com-
monly due to relative hypotension. If poor renal perfusion persists, acute tubular necrosis results. This is the
most common cause of intrinsic renal failure. The cause
of AKI is often multifactorial, however for example in
postsurgical AKI, fluid depletion, systemic inflammatory
response syndrome and nephrotoxic drugs may all play a
role. Many cases of AKI are avoidable following case review studies.
Table30.3 Acute Kidney Injury Network staging
Stage Serum creatinine level Urine output
1 1.5–2 times baseline
level or increase of
≥26.5 μmol/L
2 2.0–3 times baseline
level
3 >3.0 times baseline
level
Modified from Mehta, R.L., Kellum, J.A., Shah, S.V., Molitoris,
B.A., Ronco, C., Warnock, D.G. and Levin, A., 2007. Acute
Kidney Injury Network: report of an initiative to improve outcomes
in acute kidney injury. Critical care, 11(2), p. R31.
<0.5 mL/kg/h for
6–12 h
<0.5mL/kg/h for
≥12 h
<0.3 mL/kg/h for
≥24 h or anuria for
≥12 h
Clinical features
The symptoms of AKI are often nonspecific. AKI is commonly detected with routine blood tests. A full history
should be taken focusing on any recent infections or surgery, any possible hypovolemic episodes (e.g. from diarrhoea or vomiting) and any urinary symptoms. Ask about
any previous renal disease, diabetes and hypertension. Take
a thorough drug history, focus on NSAIDs and angiotensin
receptor blockers (ARBs) and ask about use of these drugs
in relation to any recent illness/surgery.
Your examination should focus on the cause and consequences of the renal impairment. The most important initial
assessment is to gauge the patient's volume status. Skin turgor, jugular venous pressure, postural blood pressure, heart
rate, urine output and the presence of peripheral or pulmonary oedema should be noted. If the patient is an inpatient,
a fluid balance chart may be available. You may be able to
palpate your patient’s kidneys if the patient has polycystic
kidney disease or hydronephrosis. There may be tenderness
in the renal angle in any disease that stretches the renal capsule, such as renal colic or pyelonephritis. You may be able to
palpate the bladder, with associated suprapubic discomfort,
in the presence of outflow obstruction. Examine the skin
and look for evidence of purpuric rash (e.g. in vasculitis) or
features of active lupus (e.g. malar butterfly rash).
Complications of AKI should be elicited as they may
indicate the need for dialysis or haemofiltration. Uraemia
256
Acute kidney injury
Table30.4 Causes of acute kidney injury
Prerenal injury
(ischaemic)
Renal injury Post-ischaemic acute tubular necrosis: shock, trauma, sepsis, hypoxia
Postrenal injury Renal tract obstruction: stones, tumour (prostatic or pelvic), prostatic hypertrophy, surgical mishap
Extracellular volume loss: gastrointestinal loss (e.g. severe diarrhoea or vomiting), urinary loss
(polyuria with salt-losing kidneys), burns
Intravascular volume loss or redistribution: sepsis, haemorrhage (e.g. postpartum or at operation),
hypoalbuminaemia
Decreased cardiac output: heart failure (e.g. after myocardial infarction), cardiac tamponade, cardiac
surgery
Miscellaneous: hepatorenal syndrome
Nephrotoxic acute tubular necrosis: antibiotics, analgesics, contrast media, heavy metals, solvents,
proteins
Glomerulonephritis
Acute pyelonephritis
Acute interstitial nephritis: antibiotics, analgesics, leptospirosis, viral infections
Vasculitis
Intratubular obstruction: myeloma (Bence Jones protein), urate, rhabdomyolysis
Coagulopathies: acute cortical necrosis, haemolytic uraemic syndrome, thrombotic
thrombocytopenic purpura, postpartum renal failure
Miscellaneous: malignant hypertension, hypercalcaemia
(e.g. accidental ligation of ureters), periureteric fibrosis, bladder dysfunction
Major vessel occlusion: renal artery thrombosis, renal vein thrombosis
3030
manifests itself as pericarditis, uraemic flap, twitching
and hiccups and causes itch (look for skin excoriations).
Kussmaul respiration (deep, sighing breaths) may indicate
acidosis. Respiratory examination may be consistent with
pulmonary oedema.
CLINICAL NOTES
When assessing a patient with acute kidney injury,
ask yourself:
• Are there any life-threatening complications?
• Is this renal impairment acute or chronic?
• Is this prerenal, renal or postrenal injury?
• If there is intrinsic renal failure, what is the
cause?
COMMUNICATION
Angiotensin-converting enzyme inhibitors and
angiotensin receptor blockers (ARB) act to dilate
the efferent renal arteriole, and in this way reduce
glomerular filtration pressure. They interfere with
autoregulation in the glomerulus. In the context of
systemic illness this can lead to dangerous lack of
renal perfusion and cause an acute kidney injury.
Tell all your patients to stop taking ARBs during
intercurrent illness (e.g. diarrhoea/vomiting and fever).
Investigations
Urine
• Urine analysis for blood, protein, nitrites, leucocytes.
Aim to get the urine analysis results before
catheterization.
• A midstream urine sample should be sent for
microscopy, culture and sensitivity testing.
The presence of red cell casts on microscopy is
pathognomonic of glomerulonephritis but is rarely
looked for in clinical practice.
• Send urine to the laboratory for a spot ACR or
PCR measurement to quantify urinary
protein loss.
Assessment of urinary biochemistry may help in distinguishing prerenal failure from established acute tubular necrosis. In prerenal failure the kidney avidly retains salt and
water, and hence urinary sodium level is below 20 mmol/L
and the urine is concentrated. With established acute
257