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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_2612_Библиотеки_им_академика_М_И_Перельмана
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7 Kidney medicine
Amyloid
TTP
https://t.me/med1917
Patholog ical fo lding of protein s leads to ext racellular acc umulat ion and organ dy sfunction including kidney disease. Classified according to protein: light chains in myeloma =
AL
amyloid; serum amyloid A in chronic inflammation = AA amyloid; also rare familial
Diagnosis Congo red staining on biopsy,
types.
tion. New therapies target amyloid production, aggregation, and breakdown.
Haemolytic uraemic syndrome (
Presents with a microangiopathic haemolytic anaemia (Hb <
haptoglobin, fragments on blood film), platelets, and
the glomerular capillaries (microangiopathy). In children, primarily associated with
haemorrhagic colitis due to Shiga toxin- producing E. coli (
HUS (aHUS)
is caused by dysregulation/ uncontrolled activation of complement =
5
% of
HUS
~
aemia, platelets, and
abnormalities in the complement pathway:
tation screen.
C5
. Can be precipitated by pregnancy. Diagnosis Triad of haemolytic an-
AKI
Treatment
) in England via the national a
Thrombotic th rombocytopenic purpura (
Clinical overlap with
AKI,
neurological symptoms (headache, palsies, seizure, confusion, coma), and
HUS
fever. Due to a congenital deficiency of, or acquired antibodies to,
tease which normally cleaves multimers of von Willebrand factor (v
WF
multimers cause platelet aggregation and fibrin deposition in small vessels,
v
leading to multisystem thrombotic microangiopathy.
Treatment
activity.
infusion/ exchange removes antibodies/ replaces
Corticosteroids. Consider rituximab for non- responders/ relapse.
Atherosclerotic renovascular disease
Part of systemic atheromatou s vascular disea se that incl udes cardio- , cerebro- , and
peripheral vascular disease (ask about claudication, check foot pulses),
lipids. Leads to renin– angiotensin upregulation which causes treatment- resistant
BP
and/ or a deterioration in kidney function with
heart failure (no
10
%. Diagnosis >1.5cm asymmetry in kidney size (but sensitivity and specificity).
CT
or MR angiography. Doppler studies are not consistently accurate for diagnosis.
LV
impairment on echo) with flash pulmonary oedema in up to
Tre at me nt Modification of CV risk factors: statin, aspirin, antihypertensive treat-
ment. Historically,
renin– dependent kidney perfusion and deterioration in function. However, mortality
seen with
outcomes. Large
ACE- i/ ARB
ACE- i/ ARB
so e
GFR
RCT
s of medical treatment vs revascularization have failed to show
an advantage to revascularization only considered in flash pulmonary oedema,
rapid / oligo- anuric kidney failure.
Scleroderma kidney crisis
Occurs in ~5% of systemic sclerosis. Risk with: diuse disease, anti-
III
antibodies, and <2yrs from diagnosis. Incidence with widespread use
merase
ACE- i/ ARB.
of
Diagnosis Accelerated hypertension and
collapsed glomeruli, onion- skin thickening of arterioles.
Vasodilators for digital ischaemia. May recover kidney function after many months
so listing for transplantation is delayed for up to
Sickle cell nephropathy
HbSS is associated with hyperfiltration (lower than expected creatinine) and albuminuria. Although up to
to kidney failure is usually associated with another trigger, eg papillary necrosis,
Diagnosis Clinical. Biopsy only if looking for another diagnosis, eg
infection.
without clinical cause, nephrotic syndrome.
re hydroxycarbamide and hyperfiltration. Mortality on dialysis: aim to transplant.
Care with erythropoietin- stimulating agents due to
SAP
scan. Tr ea tm en t Underlying condi-
HUS
)
AKI
STEC
with haematuria/ proteinuria. ?Evidence of
C3, C4
STEC- HUS
: supportive. a
HUS
centre, individual patient requests in rest of
, factors H and I, complement mu-
HUS
: eculizumab/ ravulizumab (anti-
TTP
)
100
g/ L,
LDH,
due to thrombosis of
) eg
O157:H7
. Atypical
STEC
. Look for
UK.
. Pentad: microangiopathic haemolytic anaemia, platelets,
ADAMTS13
pro-
WF
). Large
Diagnosis Clinical.
ADAMTS13
is a haematological emergency: get expert help. Plasma
ADAMTS13
and may be life- saving.
BP,
and
ACE- i/ ARB.
Acute decompensated
were considered contraindicated due to concern about
by <25% ‘sacrificed’ for longer- term kidney and cardiac
RNA
poly-
AKI
(e
GFR
by >30%). Biopsy:
2
years.
75
% of patients will have some degree of
Tre at me nt
ACE- i/ ARB
%
sickle cells.
Treatment
ACE- i/ ARB
CKD
, progression
AKI
. Inconsistent data
311
.
7 Kidney medicine
Kidney tubules: disorders and diuretics
RTA
https://t.me/med1917
312
Tubular disorders and the action of diuretics can be classified by the segment of
the nephron aected (
Fig 7.
13
The nephron divided into segments (proximal tubule, thick ascending loop of Henle, distal
tubule, collecting duct) with key solute movement (red).
Table 7.
8
Summary table of tubular disorders and diuretic action
Nephron segment Solute movement Tubular pathology Diuretic
Proximal tubule Reabsorption: Na+ ,
Thick ascending loop Reabsorption:
Distal tubule Reabsor ption: Na
Cortical collecting
duct
Collecting duct Excretion: water Diabetes insipidus
Proximal tubule
Physiology
Reabsorbs Na+ (~70%), bicarbonate, phosphate, amino acids, sugars, uric acid.
Patho logy
Fanconi syndrome:
DM
, phosphaturia, uricosuria, aminoaciduria, and tubular- proteinuria. Can be
impairment of proximal tubular function. Glycosuria without
genetic or acquired, eg cystinosis, Wilson disease. Phosphate loss from bone,
demineralization, and growth impairment. Treatment: underlying cause. Correct
volumetric and phosphate/ electrolytic deficiencies.
tubular acidosis
(
intact so bicarbonate usually ≥
less rare familial cause. Aetiology: light chain disease, drugs (eg tenofovir), heavy
metals. Diagnosis:
rise in urine pH to ~
IV
Diuretics
SGLT2
inhibitors: glucose reabsorption and Na+ co- transport. Na+ delivery to
macula densa leads to aerent arteriolar vasoconstriction and glomerular pres-
Mannitol: Freely filtered and reabsorbed, holding water by osmosis.
sure.
and intra-ocular pressure. Risk of pulmonary oedema if oligo/ anuric.
anhydrase inhibitor, eg acetazolamide:
excretion. Used in altitude sickness, glaucoma. Risk of nephrocalcinosis.
fig
7.13
and table
-
, phosphate,
HCO
3
sugars, amino acids
+
, K+ , Cl
Na
Excretion: K
7. 8
).
Fanconi syndrome
Proximal (type
2
)
RTA
−
Bartter syndromes Loop
+
, Cl−Gitelman syndrome Thiazide
+
+
, H
Distal (type 1)
Type 4
RTA
p
234
)
(
(RTA
= renal tubular acidosis)
SGLT2
inhibitor,
mannitol, carbonic
anhydrase inhibitor
K+ - sparing
RTA
V2
antagonists
(‘vaptan’) (
p
316
)
Proximal (type 2) renal
): failure of bicarbonate reabsorption. Distal reabsorption
12
mmol/ L. Accompanied by Fanconi syndrome un-
bicarbonate increases bicarbonate loss in urine with rapid
7.5
. Treatment: bicarbonate and potassium replacement.
Metabolic acidosis due to bicarbonate
Carbonic
ICP
7 Kidney medicine
Thick ascending loop of Henle
RTA
RTA
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Physiology
Reabsorbs Na+ (~10– 30%) and other electrolytes. Key transport via electro-
+
neutral Na
/ K+ / 2Cl− co- transporter.
Patho logy
Bartter syndromes:
Phenotype includes low- normal
2
+
, and secondary hyperparathyroidism. Fluid wasting causes activation of the
Ca
genetic mutations lead to impaired salt reabsorption.
renin– angiotensin– aldosterone axis: renin, aldosterone. Divided into subtypes
depending on transport molecule defect. Type
prostaglandin concentrations may be a feature. Treatment is with electrolyte replacement and use of
NSAID
Diuretics
Loop di uretics (eg furosemide, bumetanide):
increasing the solute load of the filtrate and reducing water resorption. Increase
excretion of water, Na
GI
from the
tract (unless it is oedematous when IV may be needed), peak concen-
tration within
+
30– 120
min. Widely used in oedematous states: heart failure, ascites,
nephrotic syndrome. Also used to treat hypercalcaemia. Side eects include hypokalaemic metabolic alkalosis, hypovolaemia, and ototoxicity.
Distal tubule
Physiology
Reabsorbs Na+ (~5– 10%) and other electrolytes. Key transport via NaCl co- transporter.
Patho logy
Gitelman syndrome:
loss of function of the NaCl co- transporter. Milder than
Bartter syndrome: usually presents in adolescence/ adulthood with incidental
finding of electrolyte abnormalities. Mimics thiazide diuretic administration.
Treat with electrolyte supplementation.
Diuretics
Thiazide (eg bendroflumethiazide) and thiazide- like diuretics (eg indapamide,
chlortalidone, metolazone):
absorption and increase water loss. Used to treat
hypokalaemia, and hypomagnesaemia. Calcium excretion is reduced (in contrast
to loop diuretics) can be used to treat recurrent kidney stones in patients with
hypercalciuria. Excretion of uric acid is reduced so care in gout. Glucose intolerance can occur (hypokalaemia and changes to renin– aldosterone are hypothesized
mechanisms) so care in
low dose, especially in the context of beneficial
Cortical collecting duct
Physiology
Acid– base and K+ homeostasis. Aldosterone acts to retain Na+ and excrete K+ .
Patho logy
1
Distal (type
genetic disease or secondary to autoimmune disease (eg Sjögren’s syndrome,
SLE
) renal tubular acidosis (
), toxins (eg lithium). Can cause, or be caused by, nephrocalcinosis (eg medullary sponge kidney, sarcoid). Leads to bone demineralization, kidney stones.
Hypokalaemia can be severe. Diagnosis: urine fails to acidify (pH >
metabolic acidosis. Treat with bicarbonate replacement and management of underlying disease.
hypoaldosteronism, eg adrenal insuciency,
Diuretics
+
- sparing amiloride, aldosterone antagonists, eg spironolactone, eplerenone:
K
used in hyperaldosteronism, hypertension, heart failure, cirrhosis, K
states. Decreased Na
Type 4
+
resorption, increased K+ resorption. Can cause K+ , acid-
osis. Oestrogenic eects with spironolactone.
BP
, K+ , metabolic alkalosis, Cl. Also hypercalciuria,
1
mimics a loop diuretic. Elevated
S (af ter v olum e rep leti on).
blo ck th e Na+ / K+ / 2Cl− co- transporter
2
+
2
, Cl−, phosphate, Mg
+
, Ca
, K+ , and H+ . Readily absorbed
inhibit the NaCl transporter decrease NaCl re-
BP
. Side eects: hyponatraemia,
DM
.
LDL
cholesterol is not significant with chronic use at
BP
red ucti on.
): failure of acid (H+ ) excretion. Primary
5.3
: hyperkalaemia and acidosis due to (real or relative)
DM, ACE-
i/
ARB
, K+ - sparing diuretics.
) despite
+
- wasting
313
7 Kidney medicine
Tubulointerstitial nephropathy and nephrotoxins
ATI N
CTIN
https://t.me/med1917
314
The tubules and the interstitium make up ~80% of the kidney. Damage to one is
usually associated with damage to the other = tubulointerstitial disease.
Acute tubulointerstitial nephritis (
Presents with
ralgia occurs in ~
AKI.
Eosinophilia in ~30%. An ‘allergic triad’ of fever, rash, and arth-
10
%. Should be considered in all cases of
obvious pre- renal or post- renal precipitant (
cell infiltrate in the interstitium ±
recognition although residual
Take a full drug history including over- the- counter and herbal preparations.
Aetiology
• Drugs: antibiotics,
• Infection: Streptococcus, Pneumococcus, Staphylococcus, Campylobacter, E. coli,
Mycoplasma,
• Autoimmune disease:
• Tubulointerstitial nephritis and uveitis syndrome
NSAID
CMV, EBV, HSV
flammation do not need to occur simultaneously. Presumed immune mediated and
responds to steroids. Rarely drug/ infection induced.
Treatment Stop causative agent/ treat underlying cause. Steroids (
Chronic tubulointerstitial nephritis (
Insidious onset and slowly progressive kidney impairment. Biopsy shows interstitial fibrosis and tubular atrophy. Most commonly due to drugs (>
Possible causes include:
• Drugs:
NSAID
S (p
315
sulfasalazine), chemotherapy (eg cisplatin).
• Infection: TB, pyelonephritis, leptospirosis,
• Immune disease: sarcoid, Sjögren’s syndrome.
• Specific nephrotoxins: lead, cadmium, mercury, aristolochic acid (p
• Haematological disorders: myeloma.
• Genetic interstitial disease.
Treatment Stop causative agent or treat underlying cause. Reduce risk of progres-
sion as per
), lithium, calcineurin inhibitors, aminosalicylates (eg mesalazine,
CKD
management:
Nephrotoxins
Many agents may be toxic to the kidneys either by direct damage to the tubules,
or by causing an interstitial nephritis. Examples (not an exhaustive list and idiosyncratic reactions are possible):
Analgesics
NSAID
S (p
Antimicrobials Aminoglycosides (p
penicillins, rifampicin, amphotericin, aciclovir.
Anticonvulsants Lamotrigine, valproate, phenytoin.
Other drugs
PPI
S, cimetidine, furosemide, thiazides,
neurin inhibitors, cisplatin.
Anaesthetic agents Methoxyflurane, enflurane.
Radiocontrast material (See p
Proteins Igs in myeloma, light chain disease, Hb in haemolysis, myoglobin in
p
rhabdomyolysis (
Crystals Urate (p
315
315
Bacteria Streptoc occi, Legion ella, Brucella, Mycoplasma, Chlamydia, TB, Salmonella,
Campylobacter, Leptospira, syphilis.
Viruses
EBV, CMV, HIV
Parasites Toxoplasma, Leishmania.
Other Ethylene glycol, radiation (p
)
p
294
tubule (‘tubulitis’). Prognosis improves with early
CKD
in up to 40%.
S,
PPI
S, diuretics, ranitidine, anticonvulsants, warfarin.
, hepatitis
SLE
, sarcoid, Sjögren’s syndrome,
315
).
A– C.
ACE- i/ ARB, BP
315
315
.)
). Biopsy shows an inflammatory
ANCA
(TINU)
: interstitial and uveal in-
)
HIV
.
control, glucose, lipids (pp
), sulfamethoxazole (in co- trimoxazole),
ACE-
i/
).
), oxalate (p
315
).
, polyomavirus, adenovirus, measles.
315
), aristolochic acid (p
AKI
for which there is no
.
RCT
evidence).
70
%) or infection.
315
).
300– 1
).
ARB
, lithium, iron, calci-
315
).
7 Kidney medicine
Analgesic nephropathy
AKI
https://t.me/med1917
Caused by
by frequency and duration of use.
lent until advanced
USS:
Non- contrast
Tre at me nt Discontinue analgesia whenever possible. Manage
NSAID
S, aspirin. Prevalence since phenacetin withdrawn. Risk determined
CKD
. Diagnosis Urinalysis: normal or sterile pyuria, proteinuria.
small and irregular kidneys. Historically classic ‘cup and spill’ appearance on
CT
: kidney mass, papillary calcification. Biopsy:
urogram if sudden flank pain to exclude obstruction from sloughed papilla.
Aminoglycosides (gentamicin > tobramycin > amikacin > streptomycin)
Toxic to renal tubules.
CKD
, volume depletion, other nephrotoxins. Presentation Typically non- oliguric
use,
AKI
1– 2 weeks after therapy. Recovery can be delayed/ incomplete. Treatment
AKI
Prevention. Single daily dose may be less nephrotoxic.
Radiocontrast- associated
Presentation
volume depletion, other nephrotoxins. Cause/ association debated: comparable rates
AKI
of
None. Pre- hydration with
in advanced
AKI
2– 7 days after IV contrast. Risk factors:
after procedures without contrast. Do not delay a necessary test. Tre atm en t
CKD
. Consider discontinuation of nephrotoxic medication for 24h pre-
and post- procedure if possible. Use lowest dose of low/ iso- osmolar contrast.
Rhabdomyolysis
Skeletal muscle breakdown with release of intracellular contents. Myoglobin is filtered causing obstruction and inflammation. Cytokines and nitric oxide cause
vasoconstriction.
immobility, hyperthermia, seizure. Muscle pain, swelling,
Diagnosis Serum myoglobin: short half- life, may be missed. Plasma CK ×5. False
Presentation History: trauma, surgery, limb ischaemia/ embolism,
+ ve blood on dipstick (ie no
Supportive. Treat hyperkalaemia (
2
+
supplementation due to myocyte entry and cell destruction. IV fluid to main-
Ca
tain volume and urine output until myoglobinuria ceased. Alkalinization of urine
hypothesized to crystallization but no
Urate nephropathy
Presentation
Uric acid crystals precipitate within the tubulointerstitium causing
inflammation. Seen in tumour lysis syndrome: tumour burden and sensitivity to
chemotherapy, phosphate. Serum uric acid is associated with
but association/ causation unclear.
allopurinol/ rasburic ase to synthesis of uric acid.
ment to uric acid (allopurinol, febuxostat).
Oxalate nephropathy
Deposition of calcium oxalate crystals (fig
interstitial nephritis/ fibrosis.
due to Crohn's,
for oxalate binding so oxalate is absorbed. High dietary oxalate, eg high- dose vit
Tre at me nt Underlying cause. Hydration. Citrate may crystallization (data).
UC
, bariatric surgery): calcium bound by free fatty acids is unavailable
Radiation nephritis
Kidney impairment due to ionizing radiation. Exclude obstruction due to strictures.
Presentation Months– years after total body irradiation, local field radiotherapy,
or targeted radionucleotide therapy. Presents with
progression to kidney failure. Prognosis linked to
peutic dose. As
CKD
(pp
300– 1
Aristolochic acid nephropathy
Progressive
CKD
due to he rbal pr eparati ons contai ning aristolo chic ac id. Presentation
Disproportionate anaemia, proteinuria, and kidney dysfunction. Biopsy: fibrosis and
tubular atrophy. Risk of urothelial malignancy ×
demic nephropathy: cluster of
acid is detected in wheat.
for malignancy. Consider therapeutic trial of steroids (limited data).
Presentation History of chronic pain. Often si-
CTIN
, papillary necrosis.
CKD
(pp
300– 1
).
USS/ CT
due to tubular necrosis. Risk factors: dose, prolonged
Check levels (p
IV
crystalloid has evidence, and care with any fluid load
RBC
on microscopy). K+ , PO
p
297
). May need dialysis/ filtration (p
RCT
evidence and may exacerbate Ca
CKD, DM,
AKI
740
).
dose of contrast,
. Red- brown urine.
−
2
+
3
, Ca
. Treatment
4
302
). Avoid
CKD
progression
2
Treatment Tumour lysis: aggressive hydration,
CKD
: no evidence for chronic treat-
7. 2
g, p
291
) in tubules causing tubular injury/
Presentation Enteric hyperoxaluria (fat malabsorption
BP
, proteinuria/ haematuria,
BP.
Treatment Use lowest thera-
), with strict BP control.
5
CKD
/ kidney failure in Balkan areas where aristolochic
Tre at me nt Avoid exposure. Trea t as
, occurs in up to 40%. Balkan en-
CKD (
pp
300– 1). Screen
IVU
.
+
.
C
.
315
7 Kidney medicine
Inherited kidney disease
ADPKD
https://t.me/med1917
316
Autosomal dominant polycystic kidney disease (
1
in
400– 1000
(~7 million worldwide). De novo mutation in ~10%. 2/ 3 will require renal
85
replacement.
50
s. Mutation in
70
s. Presentation May be clinically silent unless cysts become symptomatic due to
size/ haemorrhage (
% have mutations in
PKD2
fig
progressive kidney failure. Extrarenal: liver cysts, intracranial aneurysm
mitral valve prolapse, ovarian cyst, diverticular disease.
are common and prevalence with age so diagnostic criteria are age specific:
39
yrs ≥3 cysts, 40– 59yrs >2 cysts in each kidney give a positive predictive value
100
% for
PKD1
of
PKD2
of
and
<30 years. Liver (90% by age 50) and pancreatic cysts (~10%) support the
diagnosis. Genetic testing available but ~
use limited to diagnostic uncertainty, potential donors, and pre- implantation diag-
CT
for renal colic as cysts obscure view on
nosis.
MRI
eurysms (
SAH.
) recommended for age <65yrs if personal/ family history of aneurysm/
Trea tm en t Water intake 3– 4L/ day (if e
To l va p t a n i s r e c o m m en d e d t o s l o w p r o gr e s s i o n o f c y s t s i n
evidence of progressive disease.
ACE- i/ ARB.
Calcium channel blockers are avoided unless resistant hypertension due to
theoretical concern that Ca
infection. Haematuria usually managed conservatively. Persistent/ severe pain may
need cyst decompression. Plan for
Autosomal recessive polycystic kidney disease
1
in 20
000
, chromosome 6. Presents ante/ perinatally with kidney cysts (‘salt and
pepper’ appearance on
prognosis if neonatal respiratory distress. No specific therapy. Tolvaptan under investigation. See
OHCS
Kidney phakomatoses
Tuberous sclerosis complex
(chromosome
order with hamartoma formation in skin, brain (epilepsy), eye, heart, and lung
(see
9
) and
OHCS
p
842
). In kidney: angiomyolipomata with risk of aneurysm and haemorrhage, cystic disease in
renal cell carcinoma (rare). m
logical cell signalling and reduce tumour volume.
Von Hip pel – Lindau syndrome 1 in 36
in
VHL
gene (chromosome 3) leads to uncontrolled activation of growth factors.
Phenotype is a familial, multisystem cancer syndrome including kidney cysts and clear
cell carcinoma at mean age
inactivated in most sporadic renal cell cancers). Manage by screening for tumours.
Alport syndrome
1
in
5000
. ~80– 85% X- linked. Mutations in
code the – chain of type
disease. Average age of kidney failure in
riers’ as kidney failure in ~
lenticonus: bulging of lens on slit- lamp examination (see
the antigen in antitransplantation as graft type
ARB, BP
control, lipid management and transplantation. Newer therapies (bardoxolone,
anti- micro
GBM
RNA
, stem- cell therapy) are under investigation.
Fab r y d is ea s e
1
in 40
000– 120 000
.
enzyme - galactosidaseand some ‘carriers’. Lipid deposits in urine and on kidney biopsy (‘zebra body’).
Treatment with
IV
enzyme replacement can stabilize early kidney disease.
)
PKD1
(chromosome 4) has a slower course, often reaching
(chromosome 16) and often reach
7. 1 4
). Loin pain, visible haematuria, cyst infection, calculi, BP,
Diagnosis
PKD2
. Sensitivity is >93% for
BP
should be treated to target <
2
+
accelerates cyst proliferation (no outcome data). Treat
RRT
including pre- emptive transplantation.
USS
), congenital hepatic fibrosisportal hypertension. Poor
p
228
.
1
in
TSC2
50
6000
(chromosome 16). Variable phenotype. Multisystem dis-
%, replacement of kidney tissue leads to kidney failure,
TOR
inhibitors (eg sirolimus, everolimus) block patho-
000
40
s, ~70% risk by age 60 (
IV
collagen. Haematuria, proteinuria, and progressive kidney
30
% by 60yrs. High- tone sensorineural hearing loss. Anterior
disease (p
X-
linked. Lysosomal storage disorder due to a deficiency of the
307
) so there is a risk of anti-
IV
collagen is recognized as ‘foreign’. Managed with
A
. Proteinuria and progressive kidney disease in most
PKD1
but only 69% for diagnosis
1500
dierent mutations are described so
USS
. Screening for intracranial an-
GFR
>30) may suppress cyst growth.
CKD
stages G2 and G3 if
130/ 80
, autosomal dominant. Two genes:
, autosomal dominant (p
VHL
tumour- suppressor gene is
COL4A3, COL4A4
30– 40
, or
COL4A5
yrs. are no longer considered ‘car-
OHCS
p
842
). Type IV collagen is
GBM
ESRF
ESRF
SAH
(p
USS
. Kidney cysts
mmHg using
698
). Mutation
gene, which en-
disease following
ACE
474
TSC1
by
by
15
),
–
- i/
7 Kidney medicine
Cystinuria
https://t.me/med1917
1
in 17
000
. Autosomal recessive defect prevents reabsorption of cystine and dibasic amino acids in proximal tubule. Leads to cystinuria and cystine stone formation. May present with kidney failure requiring renal replacement. Treatment: diet,
fluid intake, and urine alkalinization to pH
makes cystine more soluble and reduces crystal and stone formation and is better
tolerated than
D
- penicillamine.
6.5– 7.0
. α- mercaptopropionyl glycine
Cystinosis
1
in
100 000– 200 000
mulation of cystine. Proximal tubule dysfunction in nephropathic forms. Fanconi
syndrome (
opathy, hypothyroidism. Oral cysteamine intralysosomal cystine and delays kidney
failure, but may be poorly tolerated due to
. Autosomal recessive lysosomal storage disorder with accu-
p
312
), and progressive kidney impairment. Also visual impairment, my-
GI
symptoms and foul smell and taste.
317
Fig 7.
14
A polycystic kidney (left) compared with a normal- sized kidney (right).
The progressive increase in size can lead to abdominal discomfort. There may be
haemorrhage into a cyst causing haematuria, or infection.
Courtesy of the
PKD
Foundation.
8
https://t.me/med1917
Haematology
Contents
A sense of humourism
The peripheral blood film
The dierential white cell count
Anaemia
324
Iron- deficiency anaemia (
Anaemia of chronic disease (
Sideroblastic anaemia
Macrocytic anaemia
B12 deficiency and pernicious
anaemia
anaemia
disorders
products
failure
doctor
(
ALL
)
352
(
CLL
)
357
(
ESR
)
368
348
350
366
330
332
344
338
340
346
364
370
An approach to haemolytic
Causes of haemolytic anaemia
Sickle cell anaemia
Thalassaemia
An approach to bleeding
Bleeding disorders
Blood transfusion and blood
Anticoagulants
Pancytopenia and bone marrow
Leukaemia and the on- call junior
Acute lymphoblastic leukaemia
Acute myeloid leukaemia (
Chronic myeloid leukaemia (
Chronic lymphocytic leukaemia
Hodgkin’s lymphoma (HL)
Non- Hodgkin’s lymphoma
Myeloproliferative disorders
Paraproteinaemia
Amyloidosis
Myeloma
Erythrocyte sedimentation rate
Plasma viscosity (PV)
Hyperviscosity syndrome
The spleen and splenectomy
Thrombophilia
Immunosuppressive drugs
336
342
364
328
368
319
326
IDA
320
AML
358
360
368
ACD
CML
372
322
)
326
)
326
334
Fig 8.
1
From Bram Stoker’s ‘Dracula’ to ‘Buy the
Vampire Slayer’ and the ‘Twilight’ series, we have
been fascinated by the undying allure of vampires.
Many times, perched by the unsuspecting patient’s
antecubital fossa in the middle of the night, armed
with a cannula and a variable degree of competency, we may have often felt like one ourselves. One
theory regarding the origin of the vampire legend
is that the hysteria arose because of outbreaks of
)
354
infectious diseases that were associated with ab-
)
356
normal bleeding. For example, it is thought that the
epidemic of supposed vampirism in the Serbian village of Medvegia in
whereby aected individuals developed disseminated intravascular coagulation (
362
to bleed from their nose and mouth.
1731
was in fact due to anthrax
Image courtesy of Eoin Kelleher.
369
DIC
), causing them
We thank Drew Provan and Siobhan Glavey, our Specialist Readers for this chapter.
8 Haematology
A sense of humourism
https://t.me/med1917
Whilst our understanding of blood has changed emphatically with the advent
of medical research, its importance in health and disease is a common theme
throughout human history and culture. Hippocrates (
the four bodily fluids, or humours (Latin umor = body fluid): blood, phlegm, and
yellow and black bile. This is not bile and phlegm as we know it; rather, it was
postulated by Fahråeus (
that humourism arose from watching blood coagulate in vitro: distilling into
1921
, the Swedish physician who pioneered the
460– 370BC) first described
ESR
, p
368
layers of bilious yellow serum floating on a scurf of white cells, with the dark redblack clot of erythrocytes lurking in the depths of the sample.
These four humours were later elaborated by Roman physician, surgeon, and
philosopher Claudius Galen (c.
ioural traits to each humour: sanguine people are warm hearted and confident,
129
– c.
201AD) who attributed physical and behav-
the phlegmatic practical and rational, those with a choleric nature are fiery and
passionate, while the melancholic (melas = black, khole = bile) are depressed yet
1
It was thought that an imbalance of any of these elements was the
creative.
source of disease, a belief which led to the wide- scale recommendation of the
removal of the excess bodily fluid: expectoration, purging, and most popularly,
bloodletting. William Harvey, Sydenham, and Dupuytren are among the famous
names who celebrated this cure, with Harvey stating that ‘daily experience satisfies us that bloodletting has a most salutary eect in many diseases, and is indeed
the foremost among all the general remedial means’. Many tools were developed
to aid this procedure, notably a collecting bowl with a convenient notch for the
antecubital fossa or neck: the predecessor of the modern kidney dish.
Such was the conviction of the healing brought about by bloodletting that
‘haematomania’ reigned despite a suspicious degree of mortality. Indeed, it may
have even killed inaugural
laryngitis he was enthusiastically bled four times by his personal physician, and
24
hours after symptom onset.
died
Eventually, the credibility of this practice waned, and by
disappeared. However, venesection still plays an important role in the management of haemochromatosis (
US
president George Washington in
p
284
) and polycythaemia rubra vera (p
1799
: on developing
1860
it had virtually
362
).
319
)
Fig 8.
2
A normal blood film, with a neutrophil, red cells, and platelets (arrows).
1
Compare these personalities with those of the
© Prof. K Lewandowski & Dr H Jastrow.
2015
anthropomorphic Pixar film Inside Out.
8 Haematology
The peripheral blood film
RBC
RBC
https://t.me/med1917
320
Many haematological (and other) diagnoses are made by careful examination of
the peripheral blood film. It is also necessary for interpretation of the
Features Include:
Acanthocytes (fig
causes: splenectomy, alcoholic liver disease, abetalipoproteinaemia, spherocytosis.
Anisocytosis Variation in
Basophilic
8.3
) Spicules on
RBC
stippling (fig
RBC
S ( unstable
RBC
membrane lipid structure);
size, eg megaloblastic anaemia, thalassaemia,
8.4
) Denatured
RNA
found in
RBC
S, indicating acceler-
ated erythropoiesis or defective Hb synthesis. Seen in lead poisoning, megaloblastic
anaemia, myelodysplasia, liver disease, haemoglobinopathy, eg thalassaemia.
Blasts Nucleated precursor cells. They should not normally appear in peripheral
blood but do in myelofibrosis, leukaemia, and malignant marrow infiltration.
Burr cells (echinocytes)
RBC
projections (less marked than in acanthocytes); fig
Cabot rings Seen in: pernicious anaemia; lead poisoning; bad infections (fig
Dimorphic picture Two populations of red cells. Seen after treatment of Fe,
B
folate deficiency, in mixed deficiency (Fe with
with primary sideroblastic anaemia, where a clone of abnormal erythroblasts produce abnormal red cells, alongside normal red cell production.
Howell– Jolly bodies
the spleen (
ease, coeliac disease, congenital,
Also in dyserythropoietic states: myelodysplasia, megaloblastic anaemia.
Hypochromia (p
thalassaemia, and sideroblastic anaemia (iron stores unusable,
Left shift Immature neutrophils released from the marrow, eg in infection (fig
DNA
fig
nuclear remnants in
8.7
). Seen post- splenectomy and in hyposplenism (eg sickle cell dis-
326
) Less dense staining of
UC
/ Crohn’s, myeloproliferative disease, amyloid).
or folate), post- transfusion, or
12
RBC
S, which are normally removed by
RBC
S due to Hb synthesis, seen in
p
362
Leukoerythroblastic film Immature cells (myelocytes, promyelocytes, metamyelo-
RBC
cytes, normoblasts) ± teardrop
tion (malignancy;
Leukaemoid reaction A marked leucocytosis (
ness, eg with infection or burns, and also in leukaemia.
Pappenheimer bodies (fig
poisoning, carcinomatosis, and post- splenectomy.
Poikilocytosis Variation in
Polychromasia
TB
; brucella; visceral leishmaniasis; parvovirus
RBC
S of dierent ages stain unevenly (young are bluer). This is a
S from haemolysis or marrow infiltration/ infec-
WCC
>50 ×
8.9
) Granules of siderocytes containing iron. Seen in lead
RBC
shape, eg in
IDA,
myelofibrosis, thalassaemia.
B19
109/ L). Seen in severe ill-
response to bleeding, haematinic replacement (ferrous sulfate,
olysis, or marrow infiltration. Reticulocyte count is raised.
Reticulocytes (Normal range: 0.8– 2%; or <85 ×
RNA
(contain
rhage, and if
Right shift Hypermature white cells: hypersegmented polymorphs (>5 lobes to nu-
cleus) seen in megaloblastic anaemia, uraemia, and liver disease. See
Rouleaux formation (fig
p
368
Schistocytes Fragmented
p
335
(
syndrome
Spherocytes Spherical cells found in hereditary spherocytosis and autoimmune
haemolytic anaemia. See
Target cells (Also known as Mexican hat cells, fig
RBC
disease, hyposplenism, thalassaemia— and, in small numbers, in
Te ar d ro p
) signifying active erythropoiesis. Increased in haemolysis, haemor-
B
, iron, or folate is given to marrow that lack these.
12
8.11
) Red cells stack on each other (causing a raised
). Seen with chronic inflammation, paraproteinaemia, and myeloma.
RBC
, fig
8.34
). Look for microangiopathic anaemia, eg
,
thrombotic thrombocytopenic purpura
S with central staining, a ring of pallor, and an outer rim of staining seen in liver
S Seen in extramedullary haematopoiesis; see leukoerythroblastic film.
S sliced by fibrin bands, in intravascular haemolysis
p
334
.
109/ L.) (fig
DIC
(p
(TTP:
p
311
8.7
and fig
8.10
) Young, larger
350
), haemolytic uraemic
), or pre- eclampsia.
8.44
IDA.
FBC
indices.
).
).
B
, folate), haem-
12
p
329
, fig
, p
339
.) These are
8.6
IDA.
8.5
.
).1
B
, or
12
IDA,
8.8
).
RBC
S
8.26
.
ESR
;
2
Cabot ‘figure- of- eight’ rings may be microtubules from mitotic spindles. It is easy to confuse them with
malaria parasites,
(
1868– 1939
clinicopathological exercises of the Massachusetts General Hospital which made the New England Journal
of Medicine so famous. He also wisely recommended that: ‘before you tell the truth to the patient, be sure you
know the truth, and that the patient wants to hear it’.
p
412
(especially if stippling gives a ‘chromatin dot’ artefact, as here). Richard Clarke Cabot
) liked diagnostic challenges: he founded the notoriously hard but beautifully presented weekly
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