Station 4 Abdomen Flashcards
(250 cards)
1
Q
How to complete your examination in abdo exam with gross ascites?
A
- cardio: raised JVP with steep x and y descent, early S3 suggestive of constrictive pericarditis
- Urine dipstick for proteinuria
- Temperature chart for fever (TB)
- Rectal examination for a rectal mass
2
Q
What is ascites
A
Pathologically accumulation of fluid in the peritoneal cavity
3
Q
How much fluid must be present before there is flank dullness?
A
1.5 L of ascitic fluid
4
Q
what are the causes of abdominal distension?
A
Fat, fluid, flatus, faeces, fetus and organ enlargement
5
Q
How would you approach a patient with ascites clinically?
A
Abdominal exam
Liver
• Look for jaundice, spleen and stigmata of CLD - cirrhosis of liver
Liver palpable and smooth - think of Budd-chiari
Liver palpable and hard and nodular - think of malignancy
Kidneys
Look for evidence of kidney failure and anasarca
heart
Look for congestive cardiac failure or constrictive pericarditis
thyroid
Look for features of hypothyroidism
If all above absent, think of
• TB peritonitis
• Intra-abdominal malignancy
——-Carcinomatosis peritonei
—— Secondaries: Liver, Colon, ovaries, pancreas
6
Q
Causes of ascites
A
Serum ascites albumin gradient >1.1g/dl = portal hypertension (97% accuracy)
- cirrhosis of liver
- Budd-Chiari
- CCF
- Constrictive pericarditis
- Malabsorption
- Meig’s syndrome
- Hypothyroidism
Serum ascites albumin gradient< 1.1g/dl
- Intra-abdominal malignancy
- TB
- Nephrotic syndrome
- Protein losing enteropathy
7
Q
Causes of ascites with Serum ascites albumin gradient >1.1g/dl
Ie. portal hypertension (97% accuracy)
A
- cirrhosis of liver
- Budd-Chiari
- CCF
- Constrictive pericarditis
- Malabsorption
- Meig’s syndrome
- Hypothyroidism
8
Q
Causes of ascites with serum ascites albumin gradient <1.1g/dl
A
- Intra-abdominal malignancy
- TB
- Nephrotic syndrome
- Protein losing enteropathy
9
Q
Pathophysiology of ascites in cirrhosis of the liver?
A
- The chief factor is splanchnic vasodilatation
- Cirrhosis leads to increased resistance to portal flow
- Leading to portal hypertension
- Portal hypertension results in local production of vasodilators, with splanchnic arterial vasodilatation
(1) Arterial underfilling
• Early stage - minimal effect on effective arterial volume as can be compensated by increase in plasma volume and cardiac output
• Later stage
- splanchnic vasodilation so marked that effectve arterial pressure falls and results in activation of vasoconstrictors and atrial natriuretic factors
- Sodium and fluid retention and expansion of plasma volume contributing to ascites
- Impaired free water execretion leading to dilutional hyponatraemia
- Renal vasoconstriction with hepatorenal syndrome
(2) Increase in splanchnic capillary pressure with lymph formation exceeding return therefore ascites
10
Q
Ix of ascites
A
(liver, renal, heart, thyroid, TB)
labs: LFT, renal panel, TFT, FBC
ascitic tap:
- cell count, albumin, serum albumin ascitic gradient, send for microbiology and cytology
imaging:
US abdo/ CT to evaluate liver (Cirrhosis, budd chiari), kidneys
Echo and ECG
CXR (TB, pleural effusion)
11
Q
ascitic tap to evaluate for ascites: what to send for
A
cell count, albumin, total protein concentration
cultures, AFB cultures
cytology
12
Q
complications of ascitic tap?
A
<0.1%: haemoperitoneum, bowel perforation
1%: abdominal wall haematoma
13
Q
management of patient with ascites secondary to liver cirrhosis?
A
treat the underlying cause
avoid alcohol or hepatotoxic medications
management of ascites:
general measures:
- salt restriction < 2g / day
- fluid restriction < 1L/day (for ascites, oedema with Na < 130)
- diuretics (spironolactone and furosemide)
- paracentesis (with albumin cover if >5L removed)
- TIPSS (Transjugular intrahepatic portosystemic shunt; high rate of shunt stenosis up to 75% at 1 year)
Liver transplant
Manage other complications of cirrhosis
14
Q
when to consider liver transplant in liver cirrhosis?
A
refractory ascites, hepatorenal syndrome, SBP
use MELD score to assign priority for liver tranplant (includes bilirubin, Cr, INR)
5 year survival rate for cirrhosis with ascites is 30-40% vs 70-80% post liver transplant
15
Q
diagnosis of spontaneous bacterial peritonitis?
A
> 250 polymorphs / ml of ascitic fluid
- commonly E coli, Klebsiella, pneumococci
- occurs due to translocation of bacteria from intestinal lumen to LNs then bacteraemia
16
Q
what features are more likely to suggest secondary peritonitis vs SBP?
A
such as peritoneal infections secondary to intraabdominal lesions, such as perforation of the hollow viscus, bowel necrosis, nonbacterial peritonitis, or penetrating infectious processes.
- loculated infection or perforated viscus
fluid findings:
- > 1000 polymorphs
- LDH > upper limit of serum
- low glucose
- high protein > 1g/L
- CEA > 5ng/ml
- ALP >240u/L
17
Q
treatment of spontaneous bacterial peritonitis?
A
3rd generation cephalosporin: ceftriaxone
IV Albumin to prevent hepatorenal syndrome
18
Q
prevention of spontaneous bacterial peritonitis?
A
ciprofloxacin, norfloxacin
19
Q
indications for SBP prophylaxis?
A
after 1 episode of SBP as recurrence as high as 70%/ year
in patients with acute variceal bleed
ascitic fluid protein concentration <1g/dl (controversial)
20
Q
what does development of ascites in a patient with liver cirrhosis mean?
A
decompensation
- occurs in 50% of patients within 10 yrs of diagnosing compensated cirrhosis
poor prognosis
- only 50% survive beyond 2 years
- poor quality of life
- increased risk of infection and renal failure
21
Q
features of ascites on abdominal examination
A
- abdominal distension +/- everted umbilicus
- positive fluid thrill with shifting dullness
22
Q
important negatives to report on detecting ascites in abdominal examination?
A
- no abdominal tenderness (SBP)
- signs of chronic liver disease and decompensation (hepatic flap, jaundice)
- signs of renal disease
- signs of hypothyroidism
- signs of malignancy
23
Q
differentials to report as potential causes of ascites?
A
cirrhosis of liver, budd chiari syndrome
nephrotic syndrome
protein losing enteropathy
congestive cardiac failure
intra-abdominal malignancy or TB
24
Q
what is cirrhosis of the liver?
A
defined pathologically
diffuse liver abnormality
fibrosis and abnormal regenerating nodules
25
causes of liver cirrhosis?
chronic ETOH ingestion
Non alcoholic fatty liver disease
Viral hepatitis - B and C
Cardiac failure
less common:
autominnue: autoimmune chronic active hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis
congenital: wilsons disease, hereditary haemochromatosis, alpha 1 AT deficiency, galatosemia, type 4 glycogen storage disease
haematological: haemolytic disease
vascular: budd-chiari
drugs: methotrexate, amiodarone, isoniazid
cryptogenic
26
drug causes of liver cirrhosis?
methotrexate, amiodarone, isoniazid
27
autoimmune conditions leading to liver cirrhosis?
autoimmune chronic active hepatitis,
primary biliary cirrhosis,
primary sclerosing cholangitis
28
vascular causes of liver cirrhosis?
budd chiari syndrome
29
congenital causes of liver cirrhosis
Wilsons disease,
hereditary haemochromatosis,
alpha 1 AT deficiency,
galatosemia,
type 4 glycogen storage disease
30
haemolytic causes of liver cirrhosis?
haemolytic disease
31
complications of cirrhosis?
portal hypertension: ascites, splenomegaly, varices
hepatorenal syndrome
hepatic encephalopathy
coagulopathy
HCC
32
features of coagulopathy in liver cirrhosis
low platelets, reduced clotting factors
33
stages of hepatic encephalopathy?
stage 1- depression, euphoria, sleep disturbance, normal eeg, may have asterixis
stage 2- lethargy, moderate confusion, asterixis present, abnormal eeg
stage 3- marked confusion, arousable, asterixis present, abnormal eeg
stage 4- coma, abnormal eeg
34
diagnosis of hepatorenal syndrome?
crcl<40
absence of other causes for renal impairment
absence of Cr improvement despite IV fluids, absence of proteinuria (0.5g/d), absence of haematuria (<50/hpf) and urinary Na < 10
35
types of hepatorenal syndrome?
type 1:
rapid deterioration in renal fn
ie. doubling of serum Cr in <2 wks to >221 umol/l
type 2: stable or slowly progressive that does not meet criteria for type 1
36
features of portal hypertension in liver cirrhosis?
ascites- tense ascites, SBP
splenomegaly-thrombocytopenia
varices- GI bleed
37
how do you stage cirrhosis of the liver?
child-pugh staging
- 5 parameters, score ranges 5 to 15
- prognostication
bilirubin (<34, 34-to 50, > 50 umol/l)
INR (<1.7, 1.7-2.3, > 2.3)
Albumin (>35, 28-35, <28)
ascites (mild, mod, severe)
encephalopathy (absent, I and II, III and IV)
38
child pugh scoring?
bilirubin (<34, 34-to 50, > 50 umol/l)
INR (<1.7, 1.7-2.3, > 2.3)
Albumin (>35, 28-35, <28)
ascites (mild, mod, severe)
encephalopathy (absent, I and II, III and IV)
A- 5 to 6 points (1 year 100%, 2 year 85%)
B: 7 to 9 (1 year 80%, 2 year 60%)
C: 10 to 15 (1 year 45%, 2 year 35%)
39
how to investigate liver cirrhosis?
confirming diagnosis: US or CT
establish aetiology: hepatitis screen, CAGE questionnaire (alcohol), liver biopsy in selected cases
prognosticate:
LFT - albumin, bilirubin
INR
complications:
endoscopy of GIT
mitotic change - US and AFP
evaluation of renal fn- urea, electrolytes, Cr
evaluation of ascitic fluid- cell count, SAAG, microbiology, cytology, AFB studies
evaluation for liver transplant
40
when should an abdominal paracentesis be done for a patient with ascites and cirrhosis?
newly diagnosed TRO SBP
symptomatic- fever, abdo pain, encephalopathy, GI bleed
41
management of liver cirrhosis?
education and counselling: regular f/u, stop ETOH drinking
manage underlying cause e.g. hep B/ C, alcoholic liver disease, NAFLD
manage complications
definitive treatment: ie. liver transplant
42
management of Hep C liver cirrhosis?
- those at risk are IVDU and blood transfusions in the past
general measures
surveillance (HCC, screen for HIV)
treatment: direct acting antivirals (sofosbuvir and daclatasvir)
43
indications of treatment for hep C
HCV RNA levels (>50 IU/ml)
Raised ALT
Bx showing fibrosis and inflammation
44
management of hepatitis B
general measures (stop alcohol, hep A vaccination)
lifelong surveillance for HCC with US and AFP
antiviral for: (entecavir, tenofovir)
- immune clearance phase (HBeAg + ALT raised)
- reactivation phase (HBeAg -, ALT raised, HBV DNA raised)
- IFN alpha
- lamivudine
45
treatment of Alcoholic liver disease?
Maddrey's discriminant function: for evaluating the severity and prognosis in alcoholic hepatitis and evaluates the efficacy of using alcoholic hepatitis steroid treatment.
- Treat with **corticosteroids** or total enteral nutrition (20-30kcal/kg/day)
**Alcohol cessation **
those with alcohol excess:
- >21u/w in males, >14u/w in females
- 100% of normal liver develops fatty liver
- 35% develop alcoholic hepatitis
- 20% develop cirrhosis
- 40% alcoholic hepatitis develop cirrhosis
46
using maddreys discrimination function to determine whether to treat with steroids in alcoholic liver disease?
PT x Bil x 4.6
>32 = severe, so. treat with steroids
If less than 32, the patient is considered to have mild to moderate alcoholic cirrhosis and would likely not benefit from the use of steroids.
47
management of complications in liver cirrhosis?
hepatic encephalopathy: treat precipitants, prevent with low protein diet, lactulose, rifaximin
hepatorenal syndrome: treat with noradrenaline infusion, terlipressin or midodrine with octreotide plus albumin infusion for 5-15 days
ascites: furosemide, spironolactone
Upper GI bleed from varices: urgent endoscopy with ligation, banding, sclerotherapy, surgery
prevention with propranolol, variceal banding
hepatocellular carcinoma: surgery, transarterial chemoembolization, radiofrequency ablation
48
management of hepatic encephalopathy?
treat the acute precipitants
prevention:
low protein diet
lactulose - works by decreasing ammonia levels in blood
rifaximin - reduces ammonia production by eliminating ammonia-producing colonic bacteria
49
management of hepatorenal syndrome
vasoconstrictors - noradrenaline, terlipressin or midodrine in combination with octreotide
+ IV albumin infusion (1g/kg on D1 then 20-40g/day)
for 5-15 days
prevention (in patients with cirrhosis and ascites):
IV albumin
50
management of upper GI bleed
ABC approach
urgent endoscopy for banding/ ligation/ sclerotherapy
surgical management if above fails
prevention: propranolol to reduce HR by 25% or to 55-60bpm
variceal banding
51
management of HCC?
MDT approach
surgical mx
transarterial chemoembolization, radiofrequency ablation
palliative
52
definitive treatment for liver cirrhosis?
liver transplant
- MARS (molecular adsorbent recirculating system) dialysis as an interim measure before liver transplant
53
what are the factors precipitating decompensation?
infection - SBP, pneumonia, UTI
GI bleed
constipation
diuretics and electrolyte imbalance
diarrhoea and vomiting
sedatives
surgery
54
what are the nail changes of hypoalbuminaemia?
leukonychia (indicating albumin < 30g/dL)
muehrcke's lines - transverse white lines
55
what are the causes of palmar erythema?
chronic liver disease
RA, thyrotoxicosis, polycythaemia
pregnancy, normal finding
56
what are the causes of anaemia in cirrhotic patients?
anaemia of chronic disease
Fe deficiency from GI bleed
haemolysis from hypersplenism
folate and B12 deficiency from poor nutrition
57
how many spider naevi should be present to be considered significant?
> 5
58
features/ signs of patient with primary biliary cholangitis as cause of chronic liver disease?
female middle age
chronic liver disease with:
pruritus
xanthelasma
generalised pigmentation
hepatosplenomegaly
assoc with sicca syndrome, arthralgia, raynauds, sclerodactyly and thyroid disease
59
stages of primary biliary cholangitis?
asymptomatic with normal LFTs (positive Abs)
asymptomatic with abnormal LFTs
symptomatic - lethargy and pruritus
decompensated
60
ix of primary biliary cholangitis?
cholestatic LFT: raised ALP
anti-mitochondrial antibodies - M2 Ab, IgM
lipid panel
other tests for chronic liver disease -LFT, INR
US abdomen
liver biopsy if diagnosis uncertain or to exclude concomitant autoimmune hepatitis/ NASH:
histology- granulomatous cholangitis
61
management of primary biliary cholangitis?
to prevent end stage liver disease and manage associated symptoms
offer patient support group
1st line: ursodeoxycholic acid
cholestyramine
fat soluble vitamins
if develops cirrhosis, manage accordingly
liver transplant
manage other co-existent autoimmune disease
62
clinical features of haemochromatosis as underlying cause of chronic liver disease?
male
slate-grey appearance, hepatomegaly
liver -cirrhosis, cancer
pancreas- DM
heart failure - CMP
pituitary dysfunction
pseudogout
63
suspecting haemochromatosis as cause of chronic liver disease, what to request for after clinical examination
urine dipstick - glucose (DM)
cardiovascular examination - may have cardiomyopathy
testicular examination - testicular atrophy (hypothalamic-pituitary dysfunction resulting in impaired gonadotropin secretion)
64
pathophysiology of hereditary haemochromatosis?
autosomal recessive
chromosome 6
HFE gene
increased Fe absorption with tissue deposition
- classically seen in those of north european ancestry
65
ix of haemochromatosis?
raised ferritin and transferrin saturation
gene testing
liver biopsy
66
management of haemochromatosis?
counselling: avoid high iron diet,
avoid alcohol
avoid shellfish as they are susceptible to Vibrio vulnificus
genetic counselling
venesection: aim ferritin 20-30, Tsat < 50%
chelation therapy if phlebotomy intolerant or contraindication e.g. severe anaemia or heart failure
Liver transplant
67
differentials of generalised pigmentation?
liver - haemochromatosis (usu males), PBC (usu females)
addison's
uraemia
chronic debilitating conditions e.g. malignancy
chronic haemolytic anaemia
68
clinical features of ulcerative colitis as cause of chronic liver disease?
skin - erythema nodosum, pyoderma gangrenosum
joint arthropathy - LL arthritis, AS, sacroiliitis
aphthous ulcers
ocular- iritis, uveitis, episcleritis
CLD; cirrhosis, chronic active hepatitis, primary sclerosing cholangitis, cholangiocarcinoma, metastatic colorectal cancer, amyloid
69
clinical features of Wilson's disease as cause of chronic liver disease?
short stature
eyes:
- KF rings (due to deposition of Copper in descemet's membrane; greenish yellow to golden brown pigmentation of limbus of cornea)
- sunflower cataract (copper deposits in the anterior and posterior capsule)
Extrapyramidal:
- tremor and chorea
- presents with difficulty writing and speaking in school
pseudogout
penicillamine complications:
- myasthenic: ptosis
- lupus: malar rash, small hand arthritis
request for urinalysis for glycosuria from proximal renal tubular acidosis
70
pathophysiology of wilsons disease?
autosomal recessive
chr 13
disorder of copper metabolism, defective copper excretion -> pathologic accumulation of cu in tissue
71
ix of wilson's disease?
low serum caeruloplasmin
increased 24h urinary copper
liver biopsy - increased Copper deposition
genetic testing (can direct whether family screening is required)
MRI brain if neurological features
72
management of wilsons disease?
counselling: low Copper diet
Cu chelation agents:
penicillamine, trientine
zinc
liver transplant may be required
SE: myasthenia, drug induced lupus
73
clinical findings in chronic liver disease?
**stigmata of chronic liver disease:**
leukonychia, clubbing, palmar erythema, spider naevi, gynaecomastia, loss of axillary hair
**decompensation:**
ascites, portal hypertension, splenmegaly
**complications:**
asterixis to suggest hepatic encephalopathy
cachexia, enlarged Cx LNs (HCC)
conjunctival pallor (GI bleed with anaemia)
**aetiology:**
- alcohol: parotidomegaly, dupuytrens contracture
- hep b: tattoos,
- hep c: surgical scar with possibility of transfusion in past
**treatment**:
abdominal tap marks
sinus bradycardia indicating use of beta blockers
74
causes of massive splenomegaly (> 8 cm)?
CML
Myelofibrosis
Polycythaemia rubra vera
chronic malaria
kala azar (visceral leishmaniasis)
Others (Gauchers, rapidly progressive lymphoma)
75
causes of moderately enlarged spleen (4 to 8 cm/ 2-4 FB)?
myeloproliferative disorders
lymphoproliferative disorders
haematological - AI, ITP, thalassaemia, hereditary spherocytosis
chronic malaria
cirrhosis
76
causes of mildly enlarged spleen (4cm, < 2 FB)?
myeloproliferative/ lymphoproliferative disorders
infection:
viral - CMV, EBV
SBE, splenic abscesses, leptospirosis, meliodosis, TB, typhoid, brucellosis (farmer)
acute malaria
infiltrative - amyloidosis, sarcoidosis
endocrine: acromegaly, thyrotoxicosis
connective tissue - SLE, Feltys (RA + neutropenia + splenomegaly)
chronic haemolytic: thalassaemia, autoimmune HA, Hereditary spherocytosis, idiopathic thrombocytopenic purpura
77
causes of tender spleen?
infective causes: viral, bacterial, malaria
acute myeloproliferative and lymphoproliferative
78
causes of splenomegaly with pallor?
essentially same as moderately enlarged spleen causes:
myeloproliferative disorders
lymphoproliferative disorders
haematological - AIHA, thalassaemia
malaria
AI- Felty's SLE
cirrhosis of the liver with portal hypertension
79
causes of splenomegaly with lymph nodes?
lymphoproliferative (CLL/ lymphoma)
infective (infectious mononucleosis, meliodosis, CMV, TB, HIV)
80
causes of massive liver?
HCC / secondaries/ myeloproliferative disorders
RV failure
alcoholic liver disease
81
causes of mild-moderate liver enlargement?
HCC / secondaries/ myeloproliferative disorders
RV failure
alcoholic liver disease
PLUS
infection:
viruses- EBV, CMV, hep A/B
bacteria- leptospirosis, meliodosis, abscesses, TB, brucellosis, syphilitic gumma
protozoal- hydatid cysts, amoebic abscess
malignancy- lymphoproliferative, myeloprolfierative, primary, secondary, adenoma from OCP
infiltrative- sarcoid (erythema nodosum, lupus pernio), amyloid, fatty liver
endocrine- amyloid, hyperthyroid
connective tissue disease
chronic haemolytic anaemia: AIHA, thalassaemia, hereditary spherocytosis
reidel's lobe
possibility of minimal CLD signs with just hepatomegaly:
PBC
haemochromatosis
82
causes of tender liver?
liver abscess/ infective (viral, bacterial, parasitic)
HCC/ secondaries
right heart failure/ budd chiari
83
causes of pulsatile liver?
tricuspid regurgitation
HCC
AVM
84
causes of hard/irregular liver?
mitotic (primary/ secondary)
macronodular cirrhosis (post hep B/C, wilsons and A1AT deficiency)
amyloidosis, hydatid cyst, granulomatous disease, gummatous disease, APCKD
85
description of hepatosplenomegaly in abdo examination?
enlarged masses in the right and left hypochondrial regions of which I am unable to get above the masses
liver enlarged:
- size, edge, surface, consistency, tender, bruit, pulsatile
spleen enlarged:
size, edge, surface, consistency, tender
kidneys not enlarged and no associated ascites
86
what peripheral examination is important in hepatosplenomegaly?
CLD stigmata, jaundice, bruises
hepatic encephalopathy
causes:
- pallor, cachexia, Cx LNs, PRV
- toxic, rashes, tonsils (Infectious mono)
- chronic ETOH ingestion
- CCF
- SBE, SLE, RA, Haemolytic anaemia
87
ix of hepatomegaly?
according to most likely aetiologies
blood ix - diagnosis
imaging
liver biopsy
88
how to describe hepatomegaly?
size- cm from right costal margin
edge- regular/ irregular
surface- smooth/ nodular
consistency- soft, film, hard
tender
pulsatile
bruit
89
examination of peripheries if there is hepatomegaly?
jaundice, bruises, stigmata of CLD, oedema of LL
hepatic flap
causes:
- cachexia, cx LNs, conjunctival pallor
- dupuytrens contracture, parotidomegaly
- toxic looking, rashes, injected throat or enlarged tonsils
- CCD- presence of raised JVP
90
hepatomegaly:
how to complete examination?
check temperature chart for fever (if infective cause is a differential)
PR exam for masses (if secondaries are a differential)
91
what are the features of an enlarged spleen in contrast to an enlarged left kidney?
palpation
- unable to get above it
- notch border
- not bimanually palpable or ballotable
percussion note over the mass is dull from left 9th rub in mid axillary line extending inferior medially in the axis of the 10th rib
inspection shows that the mass moves inferior-medially with inspiration rather than inferiorly
auscultation may reveal splenic rub
92
is a normal spleen palpable or percussible?
palpable spleen implies that it is at least twice enlarged
a normal spleen can be percussed along the 9th, 10th, 11th rib but is not percussible beyond the anterior axillary line
93
splenomegaly on examination: what aetiology to examine for
- cachexia, conjunctival pallor, cx LNs
- polycythaemia - plethoric facies, conjunctival suffusion, bone marrow biopsy scar
- toxic looking, rashes, enlarged tonsils
- splinter haemorrhages, stigmata of IE
- features of SLE, RA, chronic haemolytic anaemia
94
description of splenomegaly on examination
size: cm from left costal margin
palpable notch
edge- regular/ irregular
surface- smooth
consistency -firm
non tender
splenic rub
mention if any pallor/ lymphadenopathy
any associated hepatomegaly/ ascites/ ballotable kidneys
95
what is leukaemia?
accumulation of abnormal and immature WBCs in the bone marrow that spill into the blood resulting in bone marrow failure with pancytopenia, raised WCC and sometimes infiltration of other organs
96
what are myeloproliferative disorders?
group of clonal diseases arising from a defect in haemotopoietic stem cells
-classified according to the predominant cell lineage involved:
chronic myeloid leukaemia, polycythaemia, essential thrombocytosis, myelofibrosis
97
what is lymphoma?
replacement of normal LNs and lymphoid tissue with malignant proliferation of B or T lymphocytes
98
Reed sternberg cells
Hodgkin lymphoma
99
Tumour cells are plasma cells
multiple myeloma
100
Tumour cells have phenotype of B or T lymphocytes or their precursors?
Non Hodgkin lymphoma
-> tumour cells are mature: low-intermediate grade lymphoma
-> tumour cells are immature: high grade lymphoma
101
pathophysiology of acute leukaemia?
cells are dysplastic and immature
acquired somatic cell genetic event involving activation of oncogenes and loss of tumour suppressor gene
induced by radiation, viral infection, family hx, alkylating agents, down syndrome, wiskott-aldrich/fanconi anaemia
102
types of acute leukaemia?
acute lymphoblastic leukaemia - precursor B ALL, B cell ALL (Burkitt), T Cell ALL (usu children)
acute myeloblastic/myeloid leukaemia - several subtypes based on genetics/ phenotype (Can be any age)
103
presentation of acute leukaemia (signs/ symptoms)
bone marrow failure: anaemia, neutropenia with fever, thrombocytopenia with bruising/ bleeding
organ infiltration: tender bones, lymphadenopathy in ALL, hepatosplenomegaly, gum hypertrophy
104
ix in acute leukaemia?
FBC: normochromic anaemia, high WBC with blasts, thombocytopenia
DIC screen, renal panel, LFT including LDH, uric acid
bone marrow aspirate: hypercellular with leukaemic blasts
cytochemistry, immunophenotyping, cytogenetics, DNA analysis, morphology for further subtyping
CXR for mediastinal mass (T-ALL)
LP and CSF
pre-chemo work up:
Hep B/C/HIV
G6PD
TTE
Dental clearance
HLA typing before starting chemotherapy
105
treatment of acute leukaemia?
supportive: transfusion support, infection treatment and prophylaxis, managing complications
chemotherapy with induction, consolidation followed by allogenic bone marrow transplant
may need cranial prophylaxis for ALL
Hydrate well usually 2L/day
start allopurinol 300mg OM if no CI
106
what is hodgkins lymphoma?
characterized by reed sternberg cells which are dysplastic B cells that have not undergone apoptosis
- related to EBV infection
107
hodgkins lymphoma: clinical features?
lymphadenopathy
B symptoms: Fever, LOA/LOW, night sweats
108
management of hodgkins lymphoma?
stage 1 and 2: RT
stage 3 and 4: chemotherapy e.g. ABVD (adriamycin, bleomycin, vinblastine, dacarbazine)
109
prognosis of hodgkin lymphoma?
5 year survival 70%
110
what is non hodgkin lymphoma?
older age group, more common
proliferation of B/ T lymphocytes or their precursors largely confined to lymph nodes or bone marrow
risk factors: high fat diet, HIV, EBV
111
non hodgkins lymphoma: clinical features?
lymphadenopathy, hepatosplenomegaly
involvement of GI/ CNS/ skin and BM failure
112
management of non hodgkin lymphoma?
RT for local disease
single agent chemotherapy for low grade lymhoma e.g. chlorambucil
multiagent chemotherapy for aggressive disease
113
prognosis of non hodgkin lymphoma?
aggressive disease
survival in 5 years - 50%
114
what is chronic lymphocytic leukaemia?
commonest, mostly in males
due to accumulation of mature B lymphocytes in the bone marrow, liver, spleen, peripheral blood
disease of impaired apoptosis
115
CLL; clinical features?
Lymphocytosis on FBC
symmetric lymphadenopathy
anaemia
bleeding/bruising
infections
hepatomegaly
116
mx of CLL?
if asymptomatic, no need to treat. monitor
if symptomatic: corticosteroids, chlorambucil, cyclophosphamide, local RT
117
ix of lymphoma?
blood ix
Lymph node or bone marrow biopsy
imaging: PET CT scan for staging, CXR
118
what are the types of bone marrow transplant?
BM transplant, stem cell or cord blood transplantation
autologous or allogenic
119
what is myelodysplasia?
preleukaemic condition occurring mainly in the elderly
stem cell disorder with dysplastic growth and development in all cell lineages
- may be asymptomatic or present with unexplained anaemia/ later pancytopenia
- blasts increased but usu < 20%
- management supportive, in younger pts may consider allogenic BMT as they usually transform into acute laukaemia after 1-5 years
120
what are B symptoms
fever >38
weight loss >10% over 6 months
drenching night sweats
121
causes of hypersplenism?
vascular: splenic infarction from sickle cell anaemia, vasculitis, splenic artery thrombosis
infiltrative: amyloid, sarcoidosis
coeliac disease
autoimmune diseases
122
what is polycythaemia rubra vera?
increase in Hb and Hct due to bone marrow proliferation
- erythropoiesis is autonomous and not dependent on erythropoietin
123
polycythaemia rubra vera: clinical features?
hyperviscosity or hypermetabolism with headache, blurred vision, plethoric complexion
pruritus, sweats, splenmegaly, bleeding/ thrombosis
124
ix of polycythaemia rubra vera?
diagnosis:
- increased red cell mass (Hb, Hct), normal SaO2
- EPO raised/ subnormal
- JAK2 V617F or Exon 12 positive
- bone marrow biopsy showing hypercellularity for age with panmyelosis, inclduing erythroid, granulocytic and megakaryocytic proliferation
may have raised plt, ALP, leukocytes, high B12
exclude secondary polycythaemia with high EPO e.g. COPD, altitude, cyanotic heart disease, smoking, RCC, renal cysts, uterine fibromyomas, HCC
If splenomegaly present: higher risk of transformation to myelofibrosis. exclude transformation to MF
125
management of polycythaemia rubra vera?
maintain Hct <45% with venesection
if high risk: add hydroxyurea (myelosuppression) -> 2nd line: pegylated IFN-alpha, busulfan
Aspirin 100mg OM
if there is a hx of venous thrombosis, add systemic anticoagulation
126
prognosis of polycythaemia rubra vera?
tendency to evolve:
30% to myelofibrosis
10-15% to acute leukaemia
median survival 10-15 years
main goal of therapy is to prevent thrombohaemorrhagic complications
127
what is essential thrombocytosis?
proliferation of platelets leading to hyperviscosity
dysfunctional platelets leading to bleeding diathesis
128
essential thrombocytosis: clinical features?
splenomegaly
129
ix of essential thrombocytosis?
high plt (>450)
BM shows increased megakaryocytes
- should not meet WHO criteria for CML, PV, PMF, MDS
- presence of JAK2, CALR or MPL mutation (part of major diagnostic criteria)
- presence of clonal marker or absence of evidence of reactive thrombocytosis (minor criterion)
130
management of essential thrombocytosis?
hydroxyurea for cytoreduction
aspirin 100mg OM (start when plt<1000, to avoid in presence of extreme thrombocytosis)
if hx of venous thromboembolism, add anticoagulation
131
prognosis of essential thrombocytosis?
very low risk of leukaemic transformation (<1% at 10 years)
0.8-4.9% risk of MF transformation at 10 years
risk of thrombosis is higher in JAK2 mutated ET cases
main goal of therapy is to prevent thrombohaemorrhagic complications
132
what is myelofibrosis?
ineffective myeloid differentiation characterised by reactive bone marrow fibrosis that is de novo or 2' ET/ PRV
133
myelofibrosis; clinical features
elderly
presents with features of anaemia and massive splenomegaly due to extramedullary haematopoiesis, bleeding, gout
134
ix of myelofibrosis?
leukoerythroblastic blood film
dry BM aspirate
fibrosis on trephine
- proliferation and atypia of megakaryocytes accompanied by either reticulin and/or collagen fibrosis
135
management of myelofibrosis?
supportive with transfusion, splenectomy
136
what is chronic myeloid leukaemia?
characterized by splenomegaly, leukocytosis, philadelphia chr (translocation chr 9;22 -> hybrid gene that codes for an active tyrosine kinase that mediates clonal proliferation)
137
CML; clinical features
middle aged
presents with anaemia, splenomegaly, hypermetabolism e.g. gout
138
ix of CML?
FBC, BMA, cytogenetics, low NAP score (neutrophil alk phosphatase)
PBF: high WBC, myeloid cells, basophils
hypercellular bone marrow
philadelphia chr +ve
139
management of CML?
molecular targeted therapy
hydroxyurea as immunosuppressant
allogenic BMT
140
prognosis of CML
3 phases: chronic, accelerated, blast crisis (acute leukaemia)
mean survival 3 years
141
indications for splenectomy?
- traumatic injury with splenic rupture
- chronic haemolytic anaemia with severe anaemia, hypersplenism, abdo discomfort
- ITP with severe thrombocytopenia not controlled by immunosuppression, abdominal discomfort
- myeloproliferative disease with abdominal discomfort, severe hypersplenism
142
management of patients post splenectomy?
- vaccinations against encapsulated bacteria (meningococcus, streptococcus, haemophilus influenzae)
- risk of thrombocytosis and thrombosis therefore usually post op start sc LMWH
- prophylactic abx such as penicillin or erythromycin for > 2 yrs or lifelong
- advice to report to hospital if ill, malaria prophylaxis, travel advice, medical alert bracelet
143
what is thalassaemia?
characterised by reduced or absent production of one or more globin chains (alpha or beta, predominantly), resulting in a disruption of the ratio between alpha and non-alpha chains
144
what is thalassaemia major?
almost all thal major patients have beta thal (not alpha thal)
defined by early age of onset, transfusion dependence
age of onset:
- beta thal major presents at 3-6 mos, some later
- beta thal intermedia usually presents later than 18 mos
- alpha thal intermedia usually presents at birth as alpha chains needed for both foetal and adult Hb
transfusion dependence:
- require regular blood transfusions usu once every 3-4 w
- thal intermedia patients receive transfusions when they are symptomatic or when Hb is low
- thal minor pts do not require transfusions
145
what is thalassaemia intermedia
symptomatic thalassaemia but not requiring transfusion at least during first few years of life, and pts are able to survive into 2nd decade of life without chronic hypertransfusion therapy
146
what is thalassaemia minor?
usually asymptomatic, mild MCHC anaemia
may have slight splenomegaly
not transfusion dependent
147
what is alpha thalassaemia?
4 possible genotpes
2 genes encoding alpha globin chain on chr 16, so 4 alleles for alpha globin chain
-> deletion of one or more alpha globin genes
148
features of alpha thal 2?
one mutant allele (aa/a-)
no anaemia
FBC, peripheral blood smear, Hb electrophoresis largely normal
may have slight hypochromia and/or microcytosis
149
features of alpha thal 1 aka alpha thal minor?
2 mutant alleles: aa/-- or a-/a-
PBF shows few coarse HbH inclusion bodies on BCB stain
mild MCHC anaemia
Hb electrophoresis normal - no HbH band seen
phenotypic features slightly worse in patients with aa/-- configuration compared to a-/a- config
150
features of HbH disease?
3 mutant alleles a-/--
clinically thal intermedia phenotype
haemolytic anaemia starts in the foetus,
newborns will be anaemic and jaundiced, occ with hydrops
PBF shows many HbH inclusion bodies on BCB stain (brilliant cresyl blue)- "golf ball" appearance
Hb electrophoresis shows a fast moving HbH band
151
features of barts hydrops?
4 mutant alleles --/--
tetramer of gamma globin chains in the foetus
hydrops foetalis occurs due to high output cardiac failure,
foetus usually dies in late 2nd - mid 3rd trimester, or soon after birth
more common in asia
152
features of beta thal minor or beta thal trait?
BB^0- absence of production of beta globin in one or BB^+ - decreased production of beta globin
clinically thal minor trait with mild MCHC anaemia
PBF may show target cells
Hb electrophoresis: elevated HbA2 of 3.5 to 7%, but normal HbA2 does not rule out beta thal trait
10-15% may have asymptomatic slight hepatomegaly
153
154
haemolytic anaemia: how to complete your examination?
- look at BP chart, temperature
- blood glucose level
- CVS examination
- checking testicular size
- PR examination
155
features of chronic haemolytic anaemia on abdo examination?
hyperpigmented skin due to haemosiderosis
peripheries: jaundice (may not be present due to extramedullary haemolysis), pallor, extramedullary erythropoiesis with prominent maxilla, supraorbital ridges, dental malocclusion, gum hypertrophy
abdo: liver/spleen/kidneys, ascites, scars, iron chelation therapy marks
signs to suggest complications:
short stature for failure to thrive
loss of axillary hair for hypopituitarism
cholecystectomy scar for previous gallstones
splenectomy scar
finger prick marks for DM
CCF/ Arrhythmias
signs of chronic liver disease: if present, could be due to hep b/ c from prev transfusions, or iron overload from recurrent transfusions (DDx haemachromatosis)
156
ddx of chronic haemolytic anaemia
thalassaemia major/intermedia - likely transfusion dependent
hereditary spherocytosis or elliptocytosis
157
ix of chronic haemolytic anaemia 2' thalassaemia
for diagnosis, to establish complications
**diagnosis**: haemoglobin electrophoresis
- beta thal major/ intermedia (increased HbA2 and HbF)
genotyping - gene mutations in thalassaemia
**assess severity**
FBC: MCHC anaemia, (**Hb**) may have low Plt from hypersplenism
PBF: MCHC, anisocytosis, poikilocytosis, target cells, fragments from haemolysis, HbH inclusion bodies in alpha thal
osmotic fragility: decreased fragility
**haemolysis markers**: high retic count/ bilirubin, LDH, low haptoglobin
**complications of iron overload **
deranged LFT in cirrhosis 2' iron overload, tests of synthetic function
serum ferritin: start iron chelation therapy when >1000mcg/L
TTE or cardiac MRI to monitor iron deposition
Fasting glucose, HbA1c
Anterior pituitary hormone screen:
FSH, LH, testosterone/oestrogen
TSH free T4
ACTH, 8am cortisol
Somatotropin, IGF1
Prolactin
Bone Mineral density studies to screen for osteoporosis
158
What are HbH inclusion bodies in alpha thalassaemia
HbH is a tetramer of beta globin chains due to excess of beta globin in the RBC
159
Hb Electrophoresis for alpha thal
decreased HbA, HbA2 and HbF
HbH band seen in HbH thal
160
Hb electrophoresis for beta thal
elevated HbA2, increased HbF %
decreased HbA %
161
osmotic fragility in hereditary spherocytosis
increased
as surface area to volume ratio very low- vol cannot expand any more
162
genotyping in beta thal
point mutation in chr 11
163
genotyping in alpha thal
most commonly in SEA
deletion mutation in chr 16
164
when to determine when to start iron chelation therapy in transfusion dependent patients and how to monitor for complications
serum ferritin: start iron chelation therapy when >1000 mcg/L
MRI heart/liver once a year to monitor iron deposition
for endocrine complications
hypoPTH: Calcium, Phosphate
Thyroid function tests
DM: Blood sugar level, OGTT, urine glucose
165
management of thalassaemia major
blood transfusions for patients with thal major or intermedia with anaemia
chelation therapy with sc desferrioxamine
splenectomy if haemolytic anaemia is severe or splenomegaly is symptomatic: decreases requirements for transfusions though effect is transient
haemotopoietic cell transplantation
166
management of complications of thalassaemia major/ intermedia
from disease:
delayed puberty, gall stones, osteoporosis
from iron overload:
hypothalamus/ pituitary defect (anterior pituitary hormone replacement), hypothyroidism, DM, hypoparathyroidism, CLD, CCF
from blood transfusions, hep B, C, HIV
from iron chelation: vision and hearing loss from desferrioxamine toxicity
genetic counselling and screening
167
side effects of desferrioxamine iron chelation therapy
anaphylaxis, ototoxicity and ophthalmotoxicity
168
management of gallstones 2' thalassaemia
cholecystectomy
169
management to reduce risk of SE from desferrioxamine toxicity
monitor hearing and vision
170
management of endocrine complications due to iron overload from multiple transfusions in thalassaemia major
monitor pubertal development
screen for DM, hypothyroidism
monitor for pituitary dysfunction
171
DDx of right iliac fossa mass?
- transplanted kidneys
- carcinoma of caecum (hard mass, LNs)
- abscess: appendicular, ileocaecal
- Crohn's disease (mouth ulcers, PR for fistulas)
- ovarian tumours (in females)
- others:
- - infection: amoebiasis, TB lymphadenitis, actinomycosis
- - carcinoid
- - ectopic kidney
172
DDx left iliac fossa mass?
- transplant kidney
- colonic carcinoma (hard mass, hepatomegaly, LNs)
- diverticular abscess
- faecal mass
- ovarian tumours
- others: lymphadenitis
173
common kidney diseases leading to transplant?
DM
HTN
Glomerulonephritis
174
how does renal transplant compare with dialysis
- higher patient survival rates
- better QoL with lower hospitalization rates
175
what are the causes of transplant loss?
- patient death
- allograft failure: immunological, non-immunological, recurrence of primary disease (GN, DM), chronic allograft nephropathy
176
177
what are the immunological causes of allograft failure in transplant kidney?
acute rejection
- single most important event determining graft survival
- can result in rapid loss of graft or progression to chronic rejection or chronic allograft nephropathy
- treated with pulse steroids or anti-lymphocyte antibody therapy
chronic rejection
178
what are the non-immunological causes of allograft failure in transplant kidney?
renovascular thrombosis
ischaemia reperfusion injury
nephrotoxicity from calcineurin inhibitors
CMV, polyoma virus
DM, HTN, HLD
179
what is delayed graft function in kidney transplant?
kidney being slow to 'wake up'
defined as AKI requirement of dialysis in the first week post transplant
- main concern would be of acute rejection
180
what strategies to reduce graft loss secondary to immune mediated rejection?
- live donor better than cadaveric
- HLA matched at A, B and DR loci
- absence of pre-sensitisation: previous transplant, pregnancies, transfusions, idiopathic
- immunosuppressive therapy to reduce acute rejection: traditionally use of steroids, ciclosporin. others: calcineurin inhibitors (eg. Cyclosporin, tacrolimus), MMF, sirolimus
181
what factors increase risk of graft loss secondary to non- immune mediated rejection?
(pre-transplant)
- donor factors: old age, CVA, HTN
- Recipient factors: older, male, obese, diabetic, hypertension
182
what factors increase risk of graft loss secondary to non- immune mediated rejection? and what strategies can reduce this?
(technical factors)
increased cold ischaemia time- strategy to reduce: Living donor transplant, renoprotective preservative solutions
hyperfiltration from inadequate nephron dose: strategy would be to match size and better if male to female; use of ACEi
183
what post transplant factors increase risk of graft loss secondary to non- immune mediated rejection? and what strategies can reduce this?
**calcineurin inhibitor induced nephrotoxicity:**
- monitor levels
- use others e.g. sirolimus or MMF
**CMV infections and polyoma virus**
- prophylaxis with ganciclovir for CMV
- no Rx for polyoma virus
**HTN, HLD, DM**
- treat these, aim BP <130/80
184
what are the complications of cyclosporin?
hirsutism/ hypertrichosis
gum hypertrophy
HTN
Nephrotoxicity
Hepatotoxicity
Electrolyte abnormalities: hyperK, hyperUricaemia, hypercholesterolaemia, hypoMg
185
what are the complications of chronic steroid use?
skin -thin skin, telangiectasia, steroid purpura
cushingoid habitus
osteoporosis, AVN femoral head
peptic ulcer disease
HTN
DM
cataracts
steroid psychosis
186
signs to mention in a patient with renal impairment?
- uraemic flap
- uraemic rub
- no kussmaul's breathing (acidosis)
- no evidence of fluid overload: able to lie flat, no pedal oedema
- conjunctival pallor to suggest anaemia
evidence of RRT:
- AVF: functioning?
- transplant kidney
- permcath
- PD catheter
187
renal transplant patient: how to complete your examination?
- temperature chart for fever
- BP for hypertension
- fundoscopy for hypertensive changes
- urinalysis for haematuria, proteinuria, pyuria
188
management of renal transplant patient
education and counselling, regular follow up, compliance to medications
treat underlying cause
preparation prior to transplant
post transplant management to reduce graft loss: immunosuppressive therapy, CMV prophylaxis with ganciclovir
189
causes of a unilaterally enlarged kidney?
RCC
acute renal vein thrombosis
hypertrophy of single functioning kidney
pyonephrosis
190
causes of bilaterally enlarged kidneys with asymmetrical enlargement (one may be bigger than the other)?
APCKD
Acromegaly
DM
bilateral hydronephrosis
tuberous sclerosis, Von Hippel Lindau, Amyloidosis
191
unilateral enlarged kidney, how would you like to complete your examination
temperature chart for fever
BP for hypertension
fundoscopy for hypertensive changes
urinalysis -> but dont mention if ESRF on RRT
cardiovascular exam- for MVP and AR (assoc APCKD)
Neuro exam for stroke (III nerve palsy 2' berry aneurysm)
fhx of stroke/ aneurysm
192
what are the causes of bilateral enlarged kidneys?
APCKD
commoner:
- acromegaly (hepatosplenomegaly)
- early diabetic nephropathy
- bilateral hydronephrosis
rare:
- tuberous sclerosis
- amyloidosis
- von hippel lindau disease
193
what is von hippel lindau disease?
autosomal dominant
multiple angiomata in the retina, CNS
cysts in liver, kidneys, pancreas
assoc RCC, phaeochromocytoma
194
what are the conditions that can result in bilateral renal cysts?
- polycystic kidneys
- simple cyst
- von hippel lindau
- tuberous sclerosis
195
renal complications of APCKD?
- acute renal failure: malignant hypertension, UTI, nephrolithiasis
- chronic renal failure
- fever: UTI, pyelonephritis, pyocyst
- hypertension
- pain: chronic or acute from UTI, stones, cyst rupture, haemorrhage into cyst, upper tract obstruction
- anaemia: CRF, persistent gross haematuria
- polycythaemia: increased EPO
- malnutrition: CRF, bilateral renal enlargement with early satiety
- renal cell carcinoma (rare)
196
extra renal complications of APCKD?
cysts in liver, spleen, pancreas, ovaries; colonic diverticular disease
Cardiac: MVP (25%), AR, TR
intracranial aneurysm (III nerve palsy), SAH 3%
197
causes of hypertension in APCKD?
activation of RAA from intra renal ischaemia from architectural distortion
malignant hypertension may arise from:
renal artery stenosis from compression
renin producing cyst
198
complications of chronic renal failure?
fluid overload
electrolytes - hyperK, hyperPO4
metabolic acidosis
uraemia and its complications
hypertension
anaemia - NCNC
secondary and tertiary hyperparathyroidism
renal bone disease
199
why are patients with chronic renal failure sallow?
impaired excretion of urinary pigments combined with anaemia
200
what are the types of signs in the nails that you can detect in patients with chronic renal failure
hypoalbuminaemia: leukonychia, muehrcke's nails (paired white transverse line near distal end of nails)
renal failure:
terry's nail (distal brown arc 1mm or >)
Mee's line (single white line, also seen in arsenic poisoning)
Beau's line (non pigmented indented band = catabolic state)
201
causes of anaemia in patients with chronic renal failure?
EPO deficiency
Anaemia of chronic disease
Fe deficiency anaemia- blood loss, nutrition
Folate deficiency- nutrition
202
what is Adult polycystic kidney disease?
multisystemic, progressive disease
characterised by cyst formation and enlargement in kidneys and other organs
auto dominant with almost 100% penetrance
focal cystic dilatation of renal tubules
2 predominant types: APCKD 1 on ch 16, APCKD 2 on ch 4
203
clinical symptoms of patients with APCKD
present clinically in 3-4th decade
with
haematuria, HTN, recurrent UTI, pain and uraemia
stroke
by age 60 years, 50% will require RRT
204
causes of mortality in APCKD?
ESRF (1/3)
Stroke and other hypertensive complication (1/3)
others
205
ix of APCKD?
labs: FBC, RP, Ca, PO4, iPTH, uric acid
urinalysis
imaging:
USS abdomen
MRA for patients with high risk of aneurysm, barium enema and echocardiogram
genetic testing
206
Ravine's criteria for diagnosis of APCKD?
15-29: at least 2 cysts in 1 kidney or 1 cyst in each
30-59: at least 2 cysts in each kidney
> 60 years old: at least 4 cysts in each kidney
207
management of APCKD?
education and counselling
regular follow up
screen first degree relatives
avoid medications that can precipitate renal impairment e.g. NSAIDs, tetracycline antibiotics
medical:
hypertension- ACEi, ARB
UTI, cyst infection - usually gram neg bacteria, can use bactrim/ fluoroquinolones
pain treatment
renal failure - medical treatment or RRT
antibiotic prophylaxis
surgical management
208
surgical treatments for patients with APCKD?
pyocyst -drainage
cystectomy
nephrectomy
kidney transplant
anuerysm clipping
MVP with MR - valve replacement
209
splenomegaly in essential thrombocytosis?
- exclude transformation to myelofibrosis
- higher risk of thrombosis
210
why need to refer gastro in the case of pernicious anaemia?
increased risk of gastric cancer with autoimmune gastritis
can refer for scopes
211
causes of pancytopenia?
reduced production:
nutritional deficiencies: B12, folate, Cu
infection: HIV, viral hepatitis, parvovirus B19
myelodysplastic syndrome
aplastic anaemia: Fanconi's, Acquired
Drugs
infiltration of BM:
metastatic cancers
haematological malignancies
granulomatous disorders
myelofibrosis
storage disorders
peripheral destruction or sequestration:
DIC
TTP, HUS
AIHA
hypersplenism: 2' cirrhosis, storage diseases, lymphoma, autoimmune disorders
both: impaired production and peripheral destruction
- PNH
- HLH
- Haematological malignancies
- Transfusion assoc GvH
- SLE
212
diagnosis of myelodysplasia?
examination of blood and bone marrow showing blood cytopenias and hypercellular marrow with dysplasia, with or without excess of blasts
- prognosis depends largely on marrow blast %, number and extent of cytopenias, and cytogenetic abnormalities
213
treamtent of myelodysplasia?
low risk: growth factors, lenalidomide, transfusions
higher risk: hypomethylating agents, and whenever possible, allogeneic stem cell transplantation
214
diagnosis of HLH?
fever
splenomegaly
cytopenias (affecting >=2 lineages in peripheral blood)
hypertriglyceridaemia +/- low fibrinogen <= 1.5g/L
haemophagocytosis in BM, spleen or LN
low or absent NK cell activity
Ferritin >/=500 ug/L
soluble CD25 >/=2400 U/mL
215
Triggers of 2' HLH?
Infection e.g. EBV, CMV
Malignancy!
Rheumatologic/ autoimmune disease
Immunosuppression
Pregnancy/HELLP syndrome (rare)
in children - need to rule out primary/ familial HLH
in adults - HLH should prompt investigation for underlying malignancy
216
management of Hodgkin's lymphoma?
depending on stage of disease
- chemo/ RT or both
- PET guided approach
217
management of DLBCL, Non hodgkins lymphoma?
R CHOP
rituximab
cyclophosphamide
doxorubicin
vincristin
prednisolone
218
complications of acute leukaemia?
infection
hyperviscosity: esp if WCC High >100 x 10^9
bleeding: including fundoscopy to look for retinal bleeding
DIC
Tumour lysis syndrome
219
management of acute promyelocytic leukaemia?
All-Trans Retinoic Acid (ATRA) in 2 divided doses ASAP
correct coagulaopathy: Plt (>30 if asympto, >50 if bleeding), fibrinogen (>1.0g/L if asympto, >1.5g/L if bleeding)
for patients with high WBC (>10 x 10^9 and rising) while awaiting pre-chemo work up:
start hydroxyurea or IV cytarabine for cytoreduction
220
patients at high risk of tumour lysis syndrome?
- newly diagnosed acute leukaemia pts with TW > 100 x 10^9/L
- usually ALL > AML
- burkitt lymphoma/ leukaemia
- other aggressive lymphomas especially if LDH high at presentation
221
features of tumour lysis syndrome
LDH high
Uric acid high
K/ PO4 high
Ca low
222
management of Tumour lysis syndrome?
hydration 3-3.5L/day if no cardiac issues
good urine output (1ml/kg/h), IV furosemide if necessary
allopurinol 300mg OM OR IV rasburicase
correction of electrolytes
may require dialysis in even of severe electrolyte imbalances or acidosis
223
management of SVCO?
involve ICU team and thoracic surgeons early
IV access in lower limbs
steroids to reduce peritumoral oedema (though avoid if lymphoma suspected)
treat underlying tumour
if severe symptoms, can consider endovascular stenting
palliative RT can be considered in those not candidates for systemic treatment
224
Haemolytic anaemia + PBF showing spherocytes
DCT +ve -> AIHA
225
Haemolytic Anaemia + PBF showing agglutination?
key test: direct coombs test, cold agglutination titre
-> cold AIHA
226
Haemolytic anaemia + PBF showing shistocytes?
DIC screen, plt count
-> think of DIC/TTP/HUS
227
haemolytic anaemia + bite cells on PBF
heinz body, G6PD testing
review drug list!
consider oxidate haemolysis as cause
228
signs of extramedullary haematopoiesis?
frontal bossing
maxillary overgrowth
scoliosis
hepatosplenomegaly
229
signs and complications of chronic haemolysis?
- conjunctival pallor
- scleral icterus
- kocher's scar (previous cholecystectomy)
- right ventricular heave, loud P2 (pulmonary hypertension)
230
signs of iron overload?
- slate grey skin
- displaced apex beat (congestive cardiac failure)
- implantable cardiac device
- finger brick blood sugar marks (DM)
- diabetic dermopathy
- signs of chronic liver disease
231
how to complete your abdominal examination if suspecting thalassaemia?
- examine testes: hypogonadotrophic hypogonadism from pituitary iron loading
- urine dip for glucose
- examine CVS (iron overload)
- examine musculoskeletal system (arthritis)
232
ddx of thalassaemia?
thalassaemia major/ intermedia
hereditary spherocytosis/ elliptocytosis
autoimmune haemolytic anaemia
233
peripheral stigmata of chronic liver disease?
hyperoestrogenism: gynaecomastia, paucity of axillary hair, testicular atrophy, palmar erythema, spider naevi
alcohol: parotidomegaly, dupuytrens
hypoalbuminaemia: leuconychia
234
features of portal hypertension on examination?
ascites, caput medusae, splenomegaly
235
features of decompensation in chronic liver disease?
ascites
jaundice
encephalopathy
purpura and bruising ?coagulopathy
236
medications for IBD?
aminosalicylates for mild disease (oral or rectal sulfasalazine)
steroids + DMARDs: sulfasalazine, azathioprine, methotrexate
Biologics: anti-TNF (infliximab, adalimumab), anti IL12/23: ustekinumab
surgery
237
criteria to assess severity in ulcerative colitis?
truelove and witts
looks at no of bloody stools,
HR, temperature
Hb, ESR/CRP
238
Hereditary causes of GI polyposis?
adenomatous polyposis syndromes:
- familial adenomatous polyposis
- Gardner's (FAP variant)
hamartomatous polyposis syndrome:
- peutz jegher
- juvenile polyposis
239
evaluation of GI polyposis?
ask for personal or family history of GI polyps, cancer (colonic, extra colonic), prev scopes/ surgery
look for mucocutaneous pigmented macules (peutz jeghers)
refer GE, surgery, genetic counsellor
240
features of peutz jeghers
characteristic mucocutaneous pigmentation
- 1-5mm diameter, most commonly in perioral region and buccal mucosa
- darker and more densely clustered than common freckles
- can occur on face/ arms/ palms, soles
hamartomatous GI polyps (in 88-100%)
- stomach, small bowe, colon, rectum
- polyp infarct/ulceration/bleeding/ intestinal obstruction, intussusception
- risk of adenoma and cancer
241
management of peutz jeghers?
**genetic counselling:** autosomal dominant (10-20% de novo mutations)
- can offer genetic testing of patient and 1st degree relatives
**polyp management: **
endoscsopic polypectomy
surgery for larger polyps or if complications arise e.g. intussusception
**cancer surveillance:**
- risk of colorectal cancer
- extra colonic as well: stomach, small bowel, pancreas, breast, ovarian, uterus, cervix, testicular, lung
242
what are the scoring criteria for wilson's disease?
Leipzig criteria for diagnosis
Nazer score for prognosis
243
clinical features of haemochromatosis important to ask for?
- lethargy
- joint pains: pseudogout
- liver: cirrhosis
- pancreas: DM
- heart: CCF
- pituitary: hypogonadism
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phlebotomy in haemochromatosis: what are the target values of ferritin/ Tsat?
Tsat < 50%
Ferritin 20-30
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examination findings of patient with primary biliary cholangitis
skin: xanthelasma, xanthoma (palms, soles, extensor surfaces of knees/ elbows, ankle/wrist tendons, buttocks), excoriations
eyes: KF rings rarely (Cu retention from prolonged cholestasis)
abdomen: hepatosplenomegaly
CLD stigmata
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pathophysiology of primary biliary cholangitis?
immune and cellular injury to biliary epithelial cells, resulting in cholestasis and progressive liver fibrosis
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symptoms of primary biliary cholangitis?
fatigue, pruritus
right sided abdo discomfort
sicca complex ?sjogrens
jaundice
ask for other autoimmune conditions e.g. coeliac, T1DM, RA
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Differentials for Gynaecomastia?
- possible persistent (physiological) pubertal
- drug causes (spironolactone)
- rule out breast cancer (bloody discharge, rapid growth of lump, family history of breast ca, any lumps in armpit or neck)
- pituitary cause (any head injury/ visual field defect/ headache/ panhypopit symptoms)
- gonadal cause (ask if pubertal history is normal or not?, previous mumps orchitis? Any testicular injury?)
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examination of a patient with gynaecomastia?
- examination of chest
- axillary and cervical LN to show you are thinking of breast cancer
- Offer to check for visual field defects
- offer to examine testicles
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what medication is indicated to slow kidney function decline in adults at risk of rapidly progressing ADPKD?
Tolvaptan
(vasopressin 2 receptor antagonist)
