Case 19: I feel tired Flashcards
where is erythropoietin produced
kidneys
erythropoietin is secreted in response to what
in response to hypoxia in blood
it is transported by the blood to bone marrow where it initates erythropoiesis (the formation of new RBCs)
erythropoietin stimulates what
RBC production in the red bone marrow
where does haematopoiesis take place
begins in the yolk sac in foetus
then liver temporarily
definitively it takes place in bone marrow and thymus
what 2 components make up haem
iron and protoporphyrin
where do we get most of our iron from
leafy green vegetables
red meat
where in the digestive tract is iron absorbed
duodenum
what does total iron binding capacity mean (TIBC)
how may transferrin molecules are in the blood
what does transferrin saturations % mean
how many transferrin molecules are bound to iron
what does ferritin mean
how much iron is in storage
when do urea and creatinine typically raise relative to eGFR
reduction of 50-60% eGFR
normal length of the kidneys
11cm longitudinal
what condition is common in those with chronic kidney disease
anaemia
this contributes to their non-specific symptoms such as fatigue and shortness of breath
what is a major cause of anaemia in CKD
definitely of erythropoietin
what to give if iron is normal but someone with CKD is anaemic
erythropoietin (epoetin) treatment with a target of Hb levels between 100-120
correcting low Hb in CKD carries what risks
hypertension
thrombosis
2 primary factors which can cause renal bone disease
high phosphate levels and failure to activate vitamin D
what are active and inactive vitamin D called
inactive= 25-hydroxyvitamen D
active= 1,25-dihydroxyvitamen D
the result of raised serum phosphate levels
promotes production of hormone fibroblast growth factor 23 (FGF23) from oesteocytes and stimulates PTH release and hyperplasia of the parathyroid glands
what do FGF23 and PTH do
promote tubular phosphate excretion therefore partly compensating for reduced glomerular filtration of phosphate
what does reduced active vitamin D do
impairs the intestinal absorption of calcium
raised levels of serum phosphate complex with calcium in the extra cellular space leads to calcium phosphate deposition
both reduced absorption and increased deposition of calcium causes hypocalcaemia
this also stimulates PTH production by parathyroid glands
therefore in many patients with CKD the compensatory responses initially maintain phosphate and calcium levels at the upper and lower ends of their respective normal ranges at the expense of elevated PTH level (secondary hyperparathyroidism)
this is associated with the gradual transfer of calcium and phosphate from the bone to other tissues leading to bone resorption (osteitis fibrosa cystica)
in severe cases this may result in bony pain and increased risk of fractures
presentation of acute myeloid leukaemia
tiredness and breathlessness
recurrent infections
abnormal bleeding (gum and nose)
weight loss
vitamin D deficiency presentation
fatigue
bone pain
muscle aches
low mood
microcytic anaemia values
MCV less than 80
normocytic anaemia values
MCV 80-100
macrocytic anaemia values
MCV>100
microcytic anaemias
iron deficiency
thalassemia
sideroblastic anaemia
anemia of chronic disease
normocytic anaemias
acute blood loss
early iron deficiency anaemia
renal disease
haemolytic anaemia
malaria
sickle cell disease
aplastic anaemia
macrocytic anaemias (megaloblastic)
B12 deficiency
folate deficiency
macrocytic anaemias (non-megaloblastic)
alcoholism
liver disease
which investigation could you do for B12/folate deficiency
blood film
may show hyper segmented neutrophils
what might a blood film show in iron deficiency anaemia
pencil cells
causes of iron deficiency anaemia
diet- lack of red meat/vegetables
GI blood loss
menstruation
causes of normochromic normocytic anaemias
acute blood loss
anaemia of chronic disease or secondary anaemia
anaemia or renal failure (deficiency of erythropoietin)
what is seen under microscope with normochromic normocytic anaemia
normal red cells- even size, even shape and area of central pallor (less than 33% of the red cell diameter)
which blood type is universal donor
O -ve
old hypothesis to remember is anaemia is microcytic or macrocytic
cell divisions in developing erythrocyte stop when normal mean cell haemoglobin concentration is reached and the nucleus is extruded
as the developing erythroblasts undergo cell devisions, they become smaller
anything that reduces the production of Hb inside the developing erythrocyte will tend to encourage more cell divisions than normal (iron deficiency, thalassemia) and the erythrocyte will become smaller- microcytic
anything that delays nuclear development (B12, folate deficiencies, chemotherapy) will tend to mean that fewer cell devisions will take place before the final MCH is attained and the red cells will be larger- macrocytic
beta thalassemia minor
mild to moderate hypochromic-microcytic anemia
one abnormal beta globin chain
reduced production of Hb but usually asymptomatic
diagnosis= raised HbA2
mild splenomegaly, bronze skin, hyperplasia of bone marrow
beta thalassemia major
aka cooley anaemia
two abnormal genes
HbF affected
detected before 2 years old (need blood transfusion before this or will die)
symptoms by 4-6 months- severe anaemia, growth retardation, abnormal facial structure, pathologic fractures, osteopenia, bone deformities, hepatosplenomegaly, jaundice
the genes of alpha thalassemia
1 gene deleted= clinical silent
2 genes deleted= alpha thalassemia trait (hypochromic microcytic)
3 genes deleted= Hb H disease
4 genes deleted= Barts hydrops fetalis
other causes of iron deficiency anaemia
physiological- rapid growth, menarche, pregnancy
neonatal- prematurity, low birth weight, blood loss (early cord clamping)
diet- cows mils is the commonest cause in UK toddlers
GIT- commonest cause is NSAIDs but in older males/post menopausal women colonic and gastric cancers must be investigated
diagnosis of iron deficiency anaemia on bloods
low Hb
low MCV
low MCH
can look at ferritin but this is affected by chronic inflammation
more specific symptoms of iron deficiency anaemia
tiredness and lethargy
headache especially with activity
craving for non-food items (pica)
sore/smooth tongue
brittle nails/hair loss
koilonychia
angular stomatitis
components of Hb
iron
b12
folic acid
sources of folate in diet
cereals
liver
yeast and yeast products (marmite, Vegemite, bovril)
dark leafy green vegetables (sprouts and spinach)
baked beans
oranges and orange juice
sources of B12 in diet
cereals
liver and kidney
fish (salmon and sardines especially)
dairy (yogurt)
nutritional causes of B12 deficiency
vegan
poor diet
pregnancy
malabsorption causes of B12 deficiency
gastric- surgery, pernicious anaemia
intestine- ileal resection, fish tapeworm, tropical sprue
which type of deficiency can excess alcohol cause
folate (thiamine)
not in alcoholics that drink beer however as beer is a good source of folate
specific signs of B12 deficiency
insidious onset
mild jaundice and anaemia
glossitis
angular cheilitis/stomatitis
neuropathy- peripheral, sub-acute degeneration of the cord (SADC), optic, dementia
specific signs of folate deficiency
same as B12 but more often sensory peripheral neuropathy only
deficiency in pre-conception is associated with increased incidence of NTDs in babies
causes of macrocytosis other than megaloblastic anaemia
alcohol
pregnancy
drugs- chemotherapy, anti-folate, anti-purines, anti-HIV
liver disease
raised reticulocyte
hypothyroidism
myelodysplasia, including acquired sideroblastic anaemia
aplastic anaemia and red cell aplasia
hypoxia
myeloma and other paraproteinaemias
what is haemolytic anaemia
anaemia due to the destruction rather than underproduction of red blood cells
investigations of haemolytic anaemia
RBC with reticulocytes (reticulocytes will go up)
bilirubin and lactic dehydrogenase (LDH) will increase
Coombs test (DAT)- for immune causes
EMA-binding
glucose-6-phosphate dehydrogenase level
haemoglobin identification (HPLC)
congenital haemolytic anaemias
congenial:
disorders of the RBC membrane (hereditary ellipocytosis, hereditary spherocytosis)
RBC enzyme deficiencies (G6PD, pyruvate kinase)
RBC haemoglobin disordes (thalassaemias, sickle cell)
acquired:
autoimmune haemolysis (AIHA)
microangiopathic haemolytic anaemia (HUS, TTP, DIC)
drugs, infections, toxins
copper deficiency (Wilsons)
what is hereditary spherocytosis
an abnormality of the RBC membrane
commonest inherited red cell disorder in Northern Europeans
autosomal dominant
micro-spherocytes and polychromatic microcytes
presentation of hereditary spherocytosis
often neonatal jaundice
chronic haemolysis
jaundice
gall stones
management of hereditary spherocytosis
folic acid
splenectomy
diagnosis of hereditary spherocytosis
family history in 75%
FBC
reticulocytes
blood film
EMA binding- proteins are missing in hereditary spherocytosis meaning the resulting fluorescence is weaker- THIS IS DIAGNOSTIC
clinical findings of glucose-6-phosphate dehydrogenase deficiency
x linked
usually well between attacks
family history
history of neonatal jaundice
sudden onset of feeling unwell/lack energy, pale and yellow, backache, dark urine
drugs and food to avoid with glucose-6-phosphate dehydrogenase deficiency
fava beans
broad beans
anti-malarials
aspirin in large doses
nitrofurantoin
vitamin K
what is sickle cell disease
RBCs crescent shaped
beta globin variant
co-dominant
carriers HbAS normal
usually HbSS
auto-infarction of spleen with increased infection risk
long term management of sickle cell disease
keep warm
keep hydrated
keep regular hours
eat well
take penicillin and folic acid
pneumococcal vaccine
complications of sickle cell disease
stroke
infection/sepsis
acute chest syndrome (lungs lose their ability to breath in O2 often resulting in infection)
pulmonary hypertension
stroke prevention in sickle cell disease
primary:
detect using transcranial doppler
start regular transfusions
secondary:
following stroke or finding evidence of previous strokes on MRI
start regular blood transfusions
for both consider stem cell transplant
sickle cell disease and surgery
surgery is a problem as it increases risk of hypoxia- anaemia, dehydration, anaesthesia, blood loss
stress of surgery predisposes to sickle cell crisis- fever, post op hypoxia, post-op infection
these increase risk of painful crisis and acute chest syndrome
other long term management of sickle cell
hydroxyurea
this switches on the foetal Hb gene (HbF)
if you get this level up to 50% it will prevent majority of painful crisis
management of beta thalassemia major
long term blood transfusions and iron chelation (due to blood transfusions increasing iron) or stem cell transplantation
don’t start chelation too early- wait until ferritin is over 1000ug/L to avoid neurological an skeletal toxicity
types of autoimmune haemolytic anaemias
warm and cold (depending upon the thermal range at which the antibody is active)
diagnosis of autoimmune haemolytic anaemia
confirmed haemolysis as well as blood film
positive direct antiglobulin test (DAT/coombs test)
DAT results for warm/cold autoimmune haemolytic anaemia
positive for IgG in warm
positive for compliment in cold
secondary causes of warm autoimmune haemolytic anaemia
rheumatoid disease (SLE/lymphoma)
chronic lymphatic leukaemia
drugs- cephalosporins
ovarian teratoma
secondary causes of cold autoimmune haemolytic anaemia
EBV infection
mycoplasma pneumonia
UC
4 most common side effects of iron supplementation
GI discomfort
constipation
diarrhoea
nausea
other side effects of iron supplementation
vomiting
tooth discolouration
iron overload
faeces discolouration
hyper/hypo segmented neutrophils
neutrophils typically have 2-5 lobes
above/below this is hyper and hypo respectively
what is pernicious anaemia
rare cause of vitamin B12 deficiency
autoimmune and prevents B12 absorption
affects people ages 60-80 of Northern European descent
there is a lack of gastric protein intrinsic factor which is required for B12 absorption
the immune system produces antibodies which blocks the protein intrinsic factor from carrying B12 across the mucosal lining to be absorbed
what type of anaemia does megaloblastic anaemia cause
macrocytic anaemia from ineffective RBC production and intramedullary haemolysis
most common causes of megaloblastic anaemia
folate (B9) deficiency
cobalamin (B12 deficiency)
how is B12 deficiency treated
B12 injections every 2 months
what is another symptom of B12 deficiency
pins and needles
in hands and feet?
time frame of acute fatigue
one month or less
time frame of chronic fatigue
over 6 months
medications what can cause fatigue
benzodiazepines
antidepressants
muscle relaxants
first generation antihistamines
beta blockers
opioids
what can cause proteinuria on urine dip
pregnancy
abnormally high BP
fever
CKD
after physical exercise
UTI
nephrotic/nephritic syndrome
how to diagnose CKD based off of eGFR
the drop in eGFR must be consistent for more than 3 months therefore you need repeat bloods over months time
why is using eGFR as a single value limiting
it is based on serum creatinine so may overestimate actual GFR in patients with low muscle mass (cachexia/amputees) and underestimate actual GFR in individuals taking creatinine supplements or trimethoprim (which inhibits secretion of creatinine)
it tends to underestimate normal or near-normal function, so slightly low values shouldn’t be over-interpreted
in the elderly (most of those who have low eGFR) there is controversy about categorising people as having CKD on basis of eGFR alone particularly at stage 3A since there is little evidence of adverse outcomes when eGFR is over 45 unless there is also proteinuria
types of anaemia in those with poor kidney function
microcytic= GI bleed that can cause iron deficiency
normocytic= low erythropoietin
macrocytic= can be caused by poor nutrition in chronic renal failure resulting in B12 and folate deficiency
how can hepcidin levels cause anaemia
hepcidin is an iron-regulating peptide hormone made in the liver- it controls the delivery of iron to blood plasma from intestinal cells absorbing iron, from erythrocyte-recycling macrophages and from iron-storing hepatocytes
high levels block intestinal absorption and macrophage iron recycling, causing iron restricted erythropoiesis and anaemia
this is caused in part by inflammation involved in the pathogenesis of many kidney diseases
what is an accelerated progression of CKD defined as
sustained decrease in GFR of 25% or more and a change in GFR category within 12 months
or
a sustained decrease in GFR of 15ml/min per year
what would you do for someone with progressive chronic renal dysfunction
refer to a renal specialist clinic
what is the definition of CKD
abnormalities of kidney function or structure present for more than 3 months with implications for health
this includes all people with markers of kidney damage snd those with GFR of less than 60 on at least 2 occasions separated by a period of at least 90 days (with or without markers of kidney damage)
what GFR is considered normal/high
above 90
what GFR is considered mildly decreased
60-89
what GFR is considered mildly to moderately decreased
45-59
what GFR is considered severely decreased
30-44
what GFR is considered severely decreased
15-29
what GFR is considered kidney failure
less than 15cm
what is CKD classified on
cause
GFR category (G1-G5)
albuminuria category (A1-A3)
what factors are taken into account in the kidney failure risk equation
sex
age
eGFR
urine albumin creatinine ratio
why would you check urea and creatine in CKD
to assess for stability/progression of renal function
why would you check urinalysis and quantification of proteinuria in CKD
to assess for stability/progression of renal function
why would you check urinalysis and quantification of proteinuria in CKD
to look for haematuria and proteinuria
why would you check electrolytes in CKD
to identify hyperkalaemia and acidosis
why would you check calcium, phosphate, PTH and 25(OH)D in CKD
to assess for renal osteodystrophy
why would you check albumin in CKD
low levels may indicate malnutrition, inflammation, nephrotic syndrome
why would you check full blood count (plus Fe, ferritin, folate, B12) in CKD
to assess for anaemia
why would you check lipids, glucose and HbA1c in CKD
to assess for cardiovascular risk
why would you check renal ultrasound in CKD
if concerned about obstructive uropathy
why would you check hepatitis and HIV serology in CKD
if dialysis/transplant planned
ACEi are indicated in patients with what
HTN (under 55)
diabetes
proteinurea
when would you give antiplatelet therapy to someone with diabetes
in someone with cardiovascular disease
give aspirin/clopidogrel
what would give give to someone anaemic with T2D and CDK after replenishing iron stores
Aranesp (reengineered form of erythpropoietin
why would you give bicarbonate
to correct acidosis
in CKD is delays progression, improves erythropoietin response, protects bones and controls hyperkalaemia
why would you give calcium acetate
if giving vitamin D for secondary hyperparathyroidism, phosphate level absorption may increase
therefore, a calcium-containing phosphate binder will limit phosphate rise, improve calcium levels and thereby inhibit PTH
which diabetes treatment is good for low eGFR
GLP-1 agonist (semaglutide, dulagutide)
metformin and eGFR levels
metformin dose should be reviewed if eGFR below 45
should be stopped if eGFR below 30
when would you give vitamin D (alfacalcidol)
to treat secondary hyperparathyroidism (by inhibiting PTH)
give a calcium containing phosphate binder too as phosphate levels may rise
this improves calcium levels therefore inhibiting PTH
how are ACEi renoprotective
they dilate the efferent arteriole
this decreased intraglomerular pressure, prevents loss of protein and protects the kidneys long term
how can ACEi/ARBs effect GFR
they lower intraglomerular pressure meaning GFR can drop (haemodynamic change inside glomeruli)
can have a 25% drop in GFR from baseline, any more than this would need to stop the medication
indications to start urgent haemodialysis for CKD patients
fluid overload- intractable dependent oedema resistant to diuretics, pulmonary oedema, severe hypertension
hyperkalaemia- resistant to dietary control and medical intervention
uraemia- uraemic syndrome including anorexia, nausea, lethargy (this generally doesn’t happen until eGFR is less than 10
metabolic acidosis- chronic acidosis resistant to bicarbonate therapy
other- intractable anaemia despite erythropoietin and iron and hyperphosphatemia despite inhibitors
which is the best dialysis modality
there is no strong evidence to suggest one modality over the other
eligibility for renal transplant
all patients with end stage renal disease should be considered for transplantation
may are not suitable due to combination of comorbidity and advanced age (therefore conservative management)
no absolute age limit applies
pros of haemodialysis
4 days a week dialysis free
can be done in centre or at home
cons of haemodialysis
requires food and fluid restriction
increased risk of bleeding
tiredness post treatment
risk of catheter related infections
dialysis access at risk of stenosis and clots
risk of cardiac arrhythmias
risk of dialyser hypersensitivity
pros of peritoneal dialysis
better haemodynamic stability
can start in less than 2 weeks
preserves residual kidney function
cons of peritoneal dialysis
risk of encapsulating peritoneal sclerosis
causes constipation
risk of peritonitis
risk of ultrafiltration failure
pros of renal transplant
significant survival advantage
no dietary or fluid restrictions
cons of renal transplant
need for lifelong immunosuppression
risk of operations
risk of malignancy
what operation is done before haemodialysis can commence
arteriovenous fistula must be made for dialysis access
what happens in haemodialysis
there is diffusion of solutes from blood to dialysate across a semipermeable membrane down a concentration gradient
what happens in haemofiltration
water and solutes and filtered across a porous semipermeable membrane by a pressure gradient
replacement fluid is added to the filtered blood before it is returned to the patient
what happens in peritoneal dialysis
fluid is introduced into the abdominal cavity using a catheter
solutes diffuse from blood across the peritoneal membrane to peritoneal dialysis down a concentration gradient and the water diffuses via osmosis
what happens in renal transplantation
blood supply of transplanted kidney is anastomosed to external iliac vessels and ureter to the bladder
transplanted kidney replaces all the functions of the failed kidney
what are haemoglobinopathies
they are a group of recessively inherited genetic conditions affecting the Hb component of blood
