PHYSIOTHERAPY

BLOOD
INVESTIGATIONS

by

John Preddy
@johnpreddy93
 FAMILY GROUPS
• Some groups of blood tests link together
BLOOD INVESTIGATIONS • Combined information of grouped tests can inform conditions
• Some tests are linked to more than 1 organ
• Some tests help locate the issue
• Systems can affect each other through their input/ outputs

CATEGORIES
NORMAL VALUES
• Biochemistry (Chemical composition)
• Reference range is for 95%
• Haematology (No. , size & type of cells)
for healthy populations
WHAT ARE WE MEASURING? • 5% of population lie
1) Leakage of cellular content outside reference range
2) Clearance of waste products • Varies by age, gender &
3) Production of cells local population
4) Interaction of cells

CLINICAL REASONING CONSIDERATIONS

1) How far out of range is the result?
2) Does it fit with your patient’s symptoms?
3) Do other blood tests results agree?
4) Is the test reliable?
John Preddy 02/01/22
 FULL BLOOD COUNT

FBC

RBC WBC Platelets

Red Blood
Haemoglobin Haemocrit Lymphocytes Neutrophil Monocyte Eosinophil Basophil
Count

USES 4 MOST COMMON CAUSES OF RAISED WCC USES

• Gives us clues about • Infection • Cancer and
presence and type of • Autoimmune disorder thrombophilia
anaemia • Leukaemia indicator when
• ↓ in B12, folate and • B12 / Folate deficiency (↑ >400)
Alcoholic neuropathy, • Haemophilia if
RA & leukaemia lowered
John Preddy 02/01/22
 • Main profile consists of Hb, Haematocrit and RBC count.

Hb Hct RBC

• O2 carrying protein in RBC • Confirmatory marker of RBC • Transport oxygen, carbon

• ↓ in anaemia status dioxide and nutrients
• Marker of blood loss, hypoxia, • Proportion of whole blood between organs.
RBC PROFILE

excess glucose & SCD made up of RBCs • Lifespan of 12 weeks.

• ↓ in anaemia • Production of RBCs is
regulated by erythropoiesis
• ↑ RBC = polycythaemia found
in smokers, asthma, COPD,
spleen & kidney dysfunction
• ↓ RBC = anaemia found
in Iron, B12, Folate deficiency,
pregnancy & antacid use.

Tissue Hypoxia EPO Production

Increased RBC (Kidney)
mitigate hypoxia

RBC Production
(Bone Marrow)
John Preddy 02/01/22
 • Anaemia means reduced RBC and Hb
• Could indicate EPO or bone marrow insufficiency, blood loss or nutritional anaemia.
• MCV helps identify what type of anaemia.
ANAEMIA PROFILE
↓ MCV Normal MCV ↑ MCV

• Microcytic • Normocytic • Macrocytic

• Body does not have • Body makes RBC but cannot • Body does not have
structural components for keep them nutritional components for
correct size RBC • Blood loss/ stomach ulcers/ correct size RBC
• RBC small GI Ca • RBC large
• Iron deficiency • B12 & Folate deficiency

FBC: Hb/ RBC/ HCT = Low

Check MCV

MCV MCV MCV

<80 80-100 >100

Microcytic Normocytic Macrocytic

Check Ferritin/ TIBC Check Blood loss/ Check B12/ Folate
Urea eGFR
John Preddy 02/01/22
ANAEMIA ANALOGIES Microcytic Anaemia
• Imagine not having enough metal tent poles
(Structural Iron) for your tent (RBC).
• The tent (RBC) will not be the right size and will
be small.

Macrocytic Anaemia
• Imagine owning a new inflatable tent (RBC)
• The tent (RBC) instructions (nutritional
components) state 75 litres of air is required
make it the right size.
• If the instructions (nutritional components) have
a misprint of 95 litres, then more air is added,
and the tent (RBC) will be bigger than expected.

John Preddy 02/01/22

 FBC • B12 is a complex vitamin needed for RBC formation, tissue and cellular repair and DNA synthesis.
• B12 is found in animal proteins such as meat, fish, poultry, milk and fortified cereals.
•↓ Hb • Deficiency is more common that overload.
•↑ MCV • The body stores 3-y years' worth of B12 so deficiency more common in children and will manifest slowly in
•↓WBC & platelets adults.
• Causes include:
Serum B12 • Insufficient intake
•If ↓ deficiency indicated • Vegan
B12 DEFICIENCY
•Does not identify the cause • Increased need
• Pregnancy
•If normal, folate deficiency may be present
• Inadequate absorption
Active B12 (Holotranscobalamin) • Bacterial overgrowth in stomach and intestines
• Autoimmune conditions
•Used if Total B12 borderline low • Pernicious anaemia
•Accounts for quarter of B12 circulating in blood • Coeliac Disease
Methylmalonic Acid (MMA) • Medications
• Anta-acid
•Blood or urine test • Metformin
B12 •↑ if inadequate B12 available to tissues • Methotrexate
•Used for mild or early B12 deficiency • Chronic Disorders
Deficiency •B12 normally acts as a co-enzyme converting MM CoA to • Kidney disease
Succinyl CoA, in B12 def converts to MMA • Liver disease
• Alcoholism
Homocysteine • Deficiency leads to:
•↑ in B12 deficiency • Macrocytic (large cell) anaemia
•B12 keeps folate active, and folate ↓ homocysteine • Peripheral Neuropathy
• Sub-acute combined degeneration of the cord (SACD)
Anti-Intrinsic factor Antibody (Cause Test) • Mental changes including confusion, irritability and depression (especially older adults)
• Symptoms include:
•Protein produced in stomach that binds to vitamin B12 in the
• Confusion, memory loss, Paranoia
small bowel allowing it to be absorbed
• Dizziness
•Normally ↓ with chronic gastritis/ gastrectomy/type 1 • Fatigue, weakness
diabetes, hypoparathyroidism, Addison's disease, and
Graves' disease. • Pallor
• Rapid heart rate & Shortness of breath
Parietal Cell Antibody (Cause Test) • Sore tongue and mouth
• Tingling, numbness, and/or burning in the feet, hands, arms, and legs
•Auto-antibody against the parietal cells that produce intrinsic • Loss of appetite
factor
• Diarrhoea and/or malabsorption if there is an underlying bowel disorder
•High Sensitivity
John Preddy 02/01/22
 FBC • Folate is a complex vitamin
• It is found in green vegetables, citrus fruits, beans, peas, liver and yeast
• ↓Hb • Folate is required for normal red cell formation, tissue/ cellular repair, and
• Increased MCV DNA synthesis
FOLATE DEFICIENCY
• Folate is especially important in cell division in pregnancy
• ↓ WBC & platelets • The body stores folate for four months in the liver
Serum Folate • Unlike B12, it does not directly influence nerve function
• Causes of folate deficiency include:
• Dependant on nutrition over pre-test days • Increased need
• Falls rapidly after fasting • Pregnancy
• Malabsorption
RBC Folate • Coeliac disease
• Cystic Fibrosis
• Less affected by short term food intake • Bacterial overgrowth in stomach & intestines
• More difficult to measure • Bacteria produce folate so can raise it
• Insufficient intake
• Can be ↑ with bacterial overgrowth
• Malnutrition (needs to be consumed regularly)
B12 Metabolites Tests • Signs and symptoms
• Confusion, memory loss, Paranoia
• HoloTC • Dizziness
• MMA • Fatigue, weakness
• Pallor
• B12 converts MM CoA to Succyl CoA, when • Rapid heart rate & Shortness of breath
deficient body converts to MMA • Sore tongue and mouth
• Homocysteine • Loss of appetite
• B12 keeps folate active so when deficient can't • Deficiency leads to:
metabolise HC • Macrocytic anaemia
• Neural tube defects like spina bifida
• As Vitamin B12

John Preddy 02/01/22

 • Functional B12 Deficiency is RARE
FBC • Presents clinically like anaemic B12 deficiency
• ↓ or normal Hb • Blood tests for B12 & Folate are normal however.
FUNCTIONAL B12 DEFICIENCY
• Difference is MMA & Homocysteine are ↑ despite normal B-
• ↓ MCV vitamin levels
• Symptoms include:
Serum B12 • Confusion, memory loss, Paranoia
• Normal • Dizziness
• Fatigue, weakness
• Pallor
Serum Folate • Rapid heart rate & Shortness of breath
• Normal • Sore tongue and mouth
• Tingling, numbness, and/or burning in the feet,
hands, arms, and legs
Serum Copper • Loss of appetite
• Normal • Diarrhoea and/or malabsorption if there is
an underlying bowel disorder
MMA • Deficiency leads to:
• Macrocytic (large cell) anaemia
•↑ • Peripheral Neuropathy
• Sub-acute combined degeneration of the cord (SACD)
Homocysteine • Mental changes including confusion, irritability and
depression (especially older adults)
•↑
John Preddy 02/01/22
 • Copper is an essential mineral that the body
FBC incorporates into enzymes
• These enzymes regulate nervous system/ brain function
• ↓ WCC
COPPER IMBALANCE
• Copper is found in nuts, chocolate, mushrooms, whole
• ↓ MCV
grains, dried fruits and liver.
• ↓ Hb • Copper is absorbed from the intestines, binds to a
Copper testing protein to form ceruloplasmin and stored in the liver
• Liver excretes excess copper into bile and removed by
• Total Cu stools
• Free CU • Both Copper deficiency and excess are rare
• Caeruloplasmin Concentration • Zinc absorption is competitive with copper so excess zinc
can cause deficiency as can malnutrition
LFT
• Wilsons Disease is a genetic excess copper disorder
• Derangement due to damage from Cu excess • Signs and Symptoms include (Similar to B12 Deficiency):
•Anaemia
U&E •Nausea
• Derangement due to damage from Cu excess •Jaundice
•Fatigue
ATP7B •Behavioural changes
• Genetic test for Wilsons Disease •Tremor
•Difficulty Walking and/or swallowing
• Tertiary centre only
•Dystonia

John Preddy 02/01/22

 FBC
• Altered Hb
• Altered Haematocrit
• Altered MCH
• ↓ MCV • Iron is needed in small quantities to form RBC
IRON DEFICIENCY
• Absorbed from food in small intestine
Iron • Critical part of Hb; the protein in RBC that binds oxygen and releases
• Amount of iron in the blood it
• Consequences may be acute or chronic
Ferritin
• Overload may be seen with:
• Intracellular protein that stores Iron • Ingestion of iron tablets
• Serum concentration reflects amount of stored iron in the body as • Excessive intake
only small amount in the blood
• Mutiple blood transfusions
• Present mostly in liver so LFT needed if changed
• Also present in bone marrow and spleen
• Hereditary haemochromatosis
• Deficiency may be seen with:
Transferrin • Insufficient intake
• Blood plasma Iron transport protein • Inadequate absorption
• Produced in the liver • Increased requirements eg. Pregnancy / blood loss
• High Iron levels can lead to:
Total Iron Binding Capacity (RIBC)
• Haemochromatosis
• Measures the total capacity of your blood to bind and transport iron • Toxic accumulation in tissues and organs
• Correlates with amount of transferrin in your blood that can bind • Low iron levels can lead to:
Iron
• Anaemia
LFTs • Small RBCs (Microcytic)
• Identifies if liver damage is the cause of iron overload • Pale RBCs (Hypochromic)

HFE gene
• Gene for hemochromatosis
• Exclusively in Caucasians
• Gene affects amount of iron absorbed from gut
John Preddy 02/01/22
 • Sickel Cell Disease is genetic haematological condition
• "Hb S" polymerises (forms chains) when deoxygenated,
accumulates in RBCs, damaging the RBC membrane, changing
FBC its permeability, making it more rigid and less mobile, and
shortening its life span.
SICKLE CELL DISEASE
• RBCs then adhere and aggregate to endothelial linings causing
• ↓ RBC, Hb & Haemocrit
vaso-occlusion and damage.
• May have ↓ MCV and MCH • Normally diagnosed at birth through pin-prick testing in the UK
• May have ↓ Platelet as spleen • Migrants or refugees from at risk ethnic groups (Afro-
increases Caribbean/ malaria areas) may have not been screened at birth
so presenting with sickling symptoms later in life
• Pts can be carriers/traits or SCD
Sickle Solubility test • Common symptoms include:
• Chronic
• Anaemia
• Identifies "Hb S" if >15% total Hb • Lung disease
• Sickle nephropathy
• Test for further Ix • Pulmonary hypertension
• Does not differentiate SC trait vs SCD • AVN Hips / Shoulders
• Retinopathy
High performance liquid • Recurrent leg ulceration
• Recurrent acute pain episodes
chromatography • Typically, limbs and trunk
• Stroke
• Quantifies Hb: S, F & A • ACS
• Confirms SCD diagnosis • Sepsis
John Preddy 02/01/22
• Splenic Sequestration
 • Coeliac disease is an autoimmune disease that can present with MSK
Total IgA manifestations.
• Coeliac antibody tests help in the diagnosis of and ruling out of Coeliac
• 1st choice test
disease.
• If IgA ↓, IgG Deamidated Glidain Peptide (DGP)
GLUTEN INTOLERANCE
autoantibodies used • Blood tests detect autoantibodies that the body creates as part of an
immune response to dietary proteins (such as gluten) found in wheat, rye
IgA Tissue Transglutaminase (tTG) and barley.
• 1st choice test • Previously further biopsy of the stomach cells was required to confirm
• May be false negative if avoiding gluten pre-test diagnosis but since COVID the British Society of Gastroenterology advised
bloods only is acceptable
IgA endomysial autoantibodies (EMA) • Autoantibodies cause inflammation in the gut and result in malnutrition
• If IgA tTG is weakly positive and malabsorption.
• Typical symptoms involve the digestive tract:
Tissue transglutaminase 6 (tTG6) • Chronic diarrhoea
• Abdominal pain
• Specific for coeliac related neuropathy
• Abdominal bloating/distension
• Only available at Sheffield Institute of Gluten Related
• Oral ulceration
Disorders (SIGReD)
• Weight loss
HLA DQ2/DQ8 • Anaemia
• Additional MSK related symptoms or disorders that NICE guideline
• Highly specific test for general coeliac
20 recommend blood testing:
• Only available in tertiary settings
• Prolonged fatigue
• For patients who cannot have biopsy
• Weakness
Faecal Calprotectin • Unexplained iron, vitamin B12 or folate deficiency
• Metabolic bone disorder (reduced bone mineral density or
• Differentiate coeliac from IBS & IBD
osteomalacia)
• Raised >100 = active bowel inflammation
• Unexplained neurological symptoms (particularly peripheral
• Cross check with CRP/ESR/Neutrophil
neuropathy or ataxia)

John Preddy 02/01/22

 • WBCs are leukocytes.
• They respond to, prevent and remove infection.
• Central to the inflammatory response with CRP and TNF-a.
• There are different WBCs that help identify pathology expressed as count or percentage (WCD).
• Low WBC rare = chemotherapy, HIV, ? SLE, aplastic anaemia & Cu/Zinc deficiency.
• High WBC common = leukaemia, infection and autoimmune conditions.
WBC PROFILE

Neutrohils Lymphocytes Monocytes Baso/Eosinophils Blast Cells

• WCD 40-80% • WCD 10-20% • WCD 5% • WCD 5% • WCD <2%

• Bacterial • Viral prorection • Infiltrate • Parasite • Indicate bone
protection • B-cells = systemic protection marrow
• Driven by CRP antibody bacterial tissue • Allergy dysfunction
• Used in production • Transform into response • WBC that
autoimmune/ • T-cell = viral macrophages cannot be
inflammatory indentification • Transform into identified as
monitoring & destruction foam cells when incorrectly
• T-cells mis- combined with made
identify self- LDL • Seen in
tissue in • Foam cells for leukaemia,
autoimmune atherosclerotic myeloma &
conditions plaques lymphoma

John Preddy 02/01/22

 •↑ Proportional to degree of
cell damage at time blood
taken
CRP •Fire alarm for cell damage
•Switched off when fire-
fighters arrive

•Fire fighters for cell damage

•Respond to CRP
Neutrophil ↑ in proportion to cell
damage

•Fire engines and debris block

the street

INFLAMMATION
•↑ Due to build of
PV neutrophils, bacteria and
debris at area of cell damage
•Remain ↑ after CRP returned
to normal

•Post-fire structural
reinforcement
•Indicates amount of clotting
ESR around site of cell damage
•Slower to react than CRP
•↑ in anaemia so cross check
with MCV

•Emergency vehicles
•More fire engines = more
WCC police to control area
•Reflects inflammation
•Total CRP, PV, Neut, Lymph

John Preddy 02/01/22

 • In response to injury, local inflammatory cells (macrophages & neutrophils) release
ACUTE PHASE REACTANTS cytokines into the blood
• These cytokines are mainly IL-6, IL-1, interferon-gamma and TNF-a
• The liver responds, altering acute-phase reactants (APR)
• Acute phase reactants can be +ve or –ve, increasing or decreasing in numbers in the
blood
• Acute-phase reactants cause fever, anaemia, anorexia, somnolence, lethargy,
amyloidosis and cachexia by increasing the number of peripheral WBCs
• Below are the APR that are typically within the scope of Physiotherapists

ACUTE PHASE REACTANTS

+VE (↑) -VE (↓)
• CRP • Albumin
• Ferritin • Transferrin
• Fibrinogen
John Preddy 02/01/22
 • CRP is the "fire alarm" that goes off in the building
• The more damage there is the more alarms go off and
more fire services arrive
• CRP attracts fire engines (neutrophils/ WBC) and causes a
CRP ANALOGY

traffic jam in the street (PV)

• Once the fire-fighters are onsite, the alarms switch off
• CRP is therefore only requested acutely, with a history of
recent injury or flare up
• The structural support (fibrinogen scaffold) around the
building is ESR
• It's unlikely that a small fire, as in the specific connective
tissue damage caused by eg. RA, will result in the entire
building needing scaffold
• ESR is therefore only requested periodically, usually every
6 months
• However, following major surgery or a large muscle
trauma, ESR would be required

John Preddy 02/01/22

NEUTROPHIL ANALOGY

• Neutrophils are the "fire fighters "that respond

to CRP and cellular damage
• The more damage there is, the more fire
engines called
• A fire engine can also attend a fire without being
called out
• Perhaps because the crew have spotted a small
fire on waste ground on the way back from a call
(bacteria)

John Preddy 02/01/22

 • Plasma Viscosity increases as pressure increases in the blood.
• As the fire engines (neutrophils) and news reporters (bacterial
debris) build up in the streets, the pressure increases.
• Even after the fire alarm (CRP) has been switched off,
the engines may stay at the site for a while.
PV ANALOGY

• Neutrophils have a life span of 2 weeks, so PV may be elevated

after the initial CRP value.

• Visualise a glass filled with water.

• Imagine stirring it with a spoon and the pressure needed.
• If you added marbles to the glass, it will be harder to stir the
water as more pressure is needed.
• Now imagine the glass is inside a box so you can't see what is
causing the stirring to be harder.
• Could be stone (WBC), wool (Antibodies) or sand (bacteria).
• To determine the cause of the raised pressure checking
other blood test will be required ie. FBC

John Preddy 02/01/22

 • Following a large fire, structural reinforcement is required
• ESR indicates the amount of clotting around the damaged site
ESR ANALOGY

• If you went to the top of a tall building and dropped 3 footballs

(RBCs) and timed how long it took for them to fall, that would be
normal ESR.
• Repeat this with the footballs in a heavy sack (Fibrinogen
resulting from inflammation), the balls would drop faster.
• However, ESR can be independent from inflammation.
• If you dropped a medicine ball (Anaemic related Macrocytic
RBC) instead of footballs, ESR would raise more, and balls fall
faster
• Therefore, cross checking ESR with MCV would be needed.

John Preddy 02/01/22

 • White cells are the "emergency vehicles" (fire and
WCC ANALOGY

police cars)
• As more fire engines (neutrophils) take to the street,
the number of emergency vehicles on the street
increases.
• The WBC is the total number of white cells in
circulation.
• This reflects the total inflammation
• Cross check with each inflammatory cell to find out
more

John Preddy 02/01/22

White cells destroy

AUTOIMMUNE PROFILE
the bodys own cells

Through expression
of self-antigens
SLE SpA RA PMR Myositis Vasculitis Scleroderma Sjorgrens
/autoantibodies
• ANA +ve • 80% of pts • 80% of pts are • ↑ CRP & ESR • ↑ creatine • ANCA +ve • Scl-70 +ve • ANA +ve
• ↑ CRP &ESR HLAB27 +ve RF & Anti-CCP (>40) kinase (CK) primary highly specific • Ro and La +ve
• Sometimes RF • If HLAB27 –ve, +ve • -RF –ve • ↑ CRP and ESR • +ve RA or SLE • Ro & La +ve (ENA)
+ve consider IL23R • ↑ CRP • HLAB27 +ve • ↑ PV • FBC sometimes • RF +ve often
Which cause an • ENA 4-test or ARTSI for • ↑ Neutrophils, sometimes • ANA +ve • ↑ WCC • Anti-RNP +ve • ↓ WCC
inflammatory Panel Axial CRP, PV & • ↑ Platelets ? sometimes
• Anti-Jo-1 +ve • ↓ RBC & Hb • ↑ ESR
• Anti-Sm most • ↑ Neutrophils, Globulin • ↓ RBC ? (ENA 6-test • ANA +ve
response WCC, CRP & • HLAB27 -ve
• ↑ ESR &CRP
systemic / -ve
• ↑ CRP
specific panel) • U&E & LFT • + +ve Schirmers
ESR localised
• All 4 can be • ↑ Aldolase raised test
+ve in SLE • RF • ↑ CRP & ESR
• –ve in PSpA • ↑ U&E & LFT
Bloods aim to • +ve AxSpA
detect self-antigens/
autoantibodies

RA

SpA
SLE Seronegative 80 % sensitive Seropositive
 John Preddy 02/01/22

AUTOIMMUNE PROFILE
Inflammatory
Tests Immunological Tests
ESR CRP RF Anti-CCP HLA-B27 ANA ANCA
• 15-20% of RF • 95% specific • Present in 8% • 95% +ve in • Anti-
• Non-specific • Non-specific +ve have no for RA of general SLE neutrophil
test for test for conditions population cytoplasmic
inflammation inflammation • Prognostic > • SpA antibody
• Normal range • Normal range diagnostic for • Men 90% • Primary
RA +ve marker for
• Men 0-14 <5 systemic
• RA • Women
• Women 0- • Raised 5-15 • Sensitivity 85% +ve vasculitis
20 • Significantly 60-90% • African-
raised >15 • Specificity american
70-80% 50% +ve
• PA • PA
• -ve RF 90% • 40% +ve
specific
AUTOIMMUNE PROFILE

John Preddy 02/01/22

 • Extractable nuclear antigen panels detect the presence of one or more autoantibodies in
AUTOIMMUNE PROFILE the blood that react with protein in the cell nucleus.
• Certain autoimmune disorders are characteristically associated with 1 or more anti-ENA
antibodies.
• ENA panel consists of 4 or 6 auto-antibody tests

ENA Panel
Anti-RNP Anti-Sm Anti-SS-A Anti-SS-B Scl-70 Anti-Jo-1
• +ve result 95- • +ve in 30% of (Ro) (La) • +ve in 60% of • +ve in 30% of
100% specific SLE • +ve in 75% of • +ve in 60% of Scleroderma polymyositis
for mixed • Very Sjogren's Sjogrens • Highly • May be +ve
connective specific SLE specific with
• May be +ve • May be +ve
tissue disease marker marker for pulmonary
in SLE and in SLE and
• May be +ve Scleroderma Scleroderma Scleroderma fibrosis
in SLE &
• Rarely
Scleroderma
present
without anti-
SS-A

John Preddy 02/01/22

 • The virus inside the infected cell is too small to be detected by the
IMMUNE SYSTETM ANALOGY
white cells
• The infected cell spreads the news of the infection to the white cells
by taking a small part of the virus, called an antigen (Ag), and
"placing it on a stick" outside the cell
• This stick is called major histocompatibility complex (MHC)
• The T-Cell (type of lymphocyte) then acts like a camera and takes a
picture of the Ag/MHC.
• Having taken a photo, the T-Cell uses it to make a "wanted poster"
of the MHC/Ag villain and shows it to the B-Cell.
• The B-Cell makes Antibodies (Ab) specifically designed to counteract
the Ag. And the tailor-made Ab binds itself to the Ag.
• Once bound, a signal is activated and attracts a "posse" of
neutrophils, natural killer cells and CD4/8 cytotoxic T-Cells to destroy
the villain

• In autoimmune conditions, there is no viral infection.

• For some reason part of the cells own protein is placed on the stick.
• The same chain of normal immune events happen, including specific
antibody production.
• Eg. RF, HLA-B27 & ANA
John Preddy 02/01/22
 • Creatine kinase is an enzyme that helps detects and monitors muscle damage
• 3 forms
• CK-MB (heart muscle)
• CK-BB (brain tissue)
• CK-MM (skeletal) muscle)
MUSCLE PROFILE
• Use if pt has muscle aches or pain, tenderness, weakness and swelling after muscle damage or if
urine becomes dark-reddish-brown
• x10 the upper reference limit pathologically
• Can be accompanied by raised K+ with secondary raised urate acutely

Rhabdomyolysis Polymyositis Muscular Dystrophy Statin-related myalgia

• x10 CK • x10 CK • + x10 CK • 5-10% affected

• Red-brown urine • ↑ PV, CRP & ESR • +ve Genetic testing • Lipophilic → passively
following trauma • ANA +ve • ? Muscle biopsy diffuse into muscle
• + Raised Myogloblin • Anti-Jo-1 +ve (ENA • Occurs 1-3 yrs • Aching proximal
test 6-test panel) • ↑ Males UL/LL
• Difficulty walking and • Check LFT
stairs + falls

John Preddy 02/01/22

 ROUTINE ADDITIONAL

Parathyroid
Calcium Phosphate Vitamin D
Hormone
BONE PROFILE

Alkaline
Albumin Magnesium Oestrogen
Phosphate

Cells & Hormones Processes

Osteoclasts Osteoblasts Parathyroid hormone Magnesium

• Break down bone • Mineralise the bone • ↑ osteoclast and VitD • Required to produce
• Releasing Ca • Binding Ca to Phos to activity ↑ blood Ca/ parathyroid hormone.
from bone Phos levels • Deficiency ↓ blood
calcium.

BIPHOSPHONATES: Bind Ca to bone → suppresses osteoclast activity

Phosphate Albumin Oestrogen Calcitonin

• Forms complex with Ca • Binds to 1% of Ca • ↓ osteoclast activity • Released by thyroid

for bone structure outside of bone through calcitonin, ↓ • ↑ osteoblast activity
• Controlled by renal • ↓ Albumin with blood Ca/Phos levels = ↓ serum Ca
output/impairment malnutrition or liver • ↓ osteoclast activity
damage = ↓ Ca = ↑ serum Ca
John Preddy 02/01/22
 NORMAL BONE TURNOVER
• Osteoclasts releases Ca from
bone (A)
Metabolic processes • Ca used for metabolic
Ca Ca processes
BONE PROFILE

• Ca levels fall over few hours

Oestrogen • PTG responds, produces PTH
KIDNEY PTG
A • PTH stimulates Kidney to
release VitD3
BONE • VitD3/PTH-complex causes :
• ↑ osteoclast activity in
bone
B • ↑ Ca uptake in gut
VitD3 / PTH • ↑ reabsorption of Ca in
kidney
• ↑ Ca reabsorbed into bone by
Ca KIDNEY BONE GI osteoblasts (mineralisation)
(B)
• The speed and frequency is
suppressed by Oestrogen
John Preddy 02/01/22
 Osteoporosis
• Dysregulation of normal bone turn over.
• Through ↓ levels of oestrogen/progesterone.
• Speed & frequency of bone remodelling ↑
• More common in post-menopausal women/ LT anti-oestrogen/progesterone
BONE PROFILE

treatments (Ca)
• Bone profile: not commonly used for diagnosis or prognosis

Paget's disease
• Dysfunction of osteoclast & osteoblast pathway
• Causes unbalanced removal < mineralisation of Ca
• Bony protrusions & pain are the outcomes
• Bone profile: ↑ ALP. ↑ PTH (compensatory), ↓ Phos (2º ↑ PTH), sometimes ↑
Ca (degradation) Normal VitD, Mg, Albumin

Osteomalacia
• Vitamin D deficiency driven
• Adult rickets
• ↓ VitD = ↓ Ca = dysfunctional bone remodelling = weak bendy bones
• Causes = ↓ UV, ↓intake, ↓absorption in gut, renal impairment
• Bone profile: ↓ Ca, ↑ PTH (compensatory), ↓ Phos (2º ↑ PTH)
John Preddy 02/01/22
 • Myeloma is cancer of the B-cell Lymphocytes / plasma cells in bone marrow
• Damaged B-cells often aggregate in bone
• They produce monoclonal globulin protein called a Bence-Jones Protein
• Types of globulins produced by B-cells can be assessed by electrophoresis and
MYELOMA PROFILE
differentiated between different types of myeloma and leukaemia
• Normal antibodies have 2 components: heavy and light chains
• Some faulty B-cells produce antibodies that have only the light chain
• Free Light Chains (FLC) are measured in blood (paraprotein/FLC) or urine (Bence-Jones)

WBC Globulin PV ESR Bone profile LDH

• + Raised as more • + Raised from Ab • + Raised due to • + Raised as • + Raised calcium • Lactate
B-cells production more globulins clotting raised • Normal dehydrogenase
• Albumin = and B-cells • + Platelets may Parathyroid • + Raised due
normal also be raised hormone & Vit D to high
metabolic
rate of Ca cells

Serum Protein
Electrophoresis
• Diagnostic (blood sample)
• Separates blood proteins
• Large amounts of M-protein
(IgG/A)
• Normal Ig decrease
• Albumin normal
Serum Free Light Chains
• Monitoring (blood)
• Increased Kappa or Lambda
FLC
Urine Bence-Jones Protein
• Rather than blood FLC
• Urine sample needed
B2M
• Beta-2 microglobulin
• Tumour marker for blood
cancers (Myeloma /
lymphoma)
• Gives info on amount of
cancer present and spread
• Prognositic

John Preddy 02/01/22

 • Imagine a B-cell called Bob.
• Bob makes a certain type of normal antibody.
MYELOMA ANALOGY
• Once Bob dies, Bob's children will also only ever make the
same antibody, and the grandkids and the great-
grandchildren likewise, as they are all clones of the
original Bob.
• Imagine we also have B-cells called Brenda, Bruno, Bill,
Bella, Beatrice, Bellatrix, Bethan and Bomber.
• Each of these B-cells produces a different antibody so we
have "polyclonal" antibody production. All their clones
will continue to produce these different antibodies.
• But if the bone marrow goes wrong and only makes Bobs,
then we may switch from a " polyclonal" profile to a
"monoclonal" profile, as only one type of B-cell is being
produced.
• Here the monoclonal protein Bob produces in Bence-
Jones paraprotein.
John Preddy 02/01/22
 • Tumour markers are usually proteins produced by the body in response to cancer growth or
the cancer tissue itself
• Detection and measurement can:
• Aid diagnosis
TUMOUR MARKEES
• Predict and monitor response to treatment
• Detect reoccurrence

Calcitonin AFP CA 125 CA 15-3 Lung Ca

• Indicative of rare • Alpha-fetoprotein • Cancer antigen 125 • Raised in • CA 15-3

thyroid Ca • ↑ Liver Ca • Raised in 80% of metastasised Breast • CA19-9
• C-cell hyperplasia • ↑ Testes Ca Ovarian Ca Ca • CEA
• Medullary thyroid • Raised in
Ca endometriosis

Monoclonal
Platelets Lactate dehydrogenase B2M PSA
Immunoglobulins
•Unexplained raise >400 •+ Raised due to high •Raised in Mutiple •Beta-2microglobulin •Raised in prostate Ca
•Indicates LEGO-C Ca metabolic rate of Ca cells myeloma •Tumour marker for •Raised in benign
•Raised in MGUS blood cancers (Myeloma prostate hyperplasia
/ lymphoma) (BPH)
•Gives info on amount of
cancer present and
spread
•Prognostic

John Preddy 02/01/22

 • Kidneys can refer pain into the lateral flanks, low back, lateral hips and groins

Na+
• Electrolyte that controls water balance in the blood
• Concentration = Mass of Na+ / Volume of water
• High if excess ingested or vomiting, or both, or CKD
KIDNEY PROFILE

K+
• Intracellular electrolyte that controls calcium channels
• Essential for muscle and nerve function
• Low after vomiting & diarrhoea, liquorice or ileostomy
• High after muscle destruction, acidosis & renal dysfunction

Urea
• Kidney normally excretes
• Builds up with acute kidney dysfunction

Creatinine
• Normally less prevalent
• Takes longer to see changes in levels
• Unless the problem is severe
• Elevated when chronic kidney dysfunction

Urate
• Released when a WBC is broken down
• If excess input/ inadequate removal then raises = gout
• In gout, uric acid-urate form MSU in joint so may take a while for urate in
blood to raise. Request 4-6 after attack

John Preddy 02/01/22

 Liver • Store iron, B12, glucose
• Produce cholesterol, CRP, fibrinogen & albumin
• Detoxify endogenous & exogenous toxins

Function • CAN BE A SOURCE OF RIGHT UPPER QUADRANT

ABDO & RIGHT SHOULDER PAIN
LIVER PROFILE

Bilirubin AMINOTRANSFERASES ALP Albumin GGT

• Breakdown product of • Leak out when liver • Enzyme in the blood • Protein made by the • Gamma-
RBC cells damage • Affected by liver, liver glutamyltransferase
• Gives us clues about • More than 1.5 bone, kidney & • Decrease with liver • Alchohol marker
the livers plumbing normal pathological placenta damage • Raised for 5 days
• Rises before enzymes • AST • Correlate with other • Transports calcium following alchohol
do • Acute liver damage profiles • Contributes to • Check FBC, MCV,
• Needs to be • Raised in ETOH • Raised 2-3x = biliary osmotic stability serum/RBC Folate,
considered with • Used in obstruction • Linked to oedema & homocysteine and
other blood tests to conjucntion with renal function MMA for Folate
see if the problem is ALT • Precursor for deficiency
in the liver or antibody production
elsewhere • ALT
• Acute and chronic
liver damage
• Raised in viral Hep

John Preddy 02/01/22

 Pancreas • Produces digestive juices, insulin & other
hormones
• CAN BE A SOURCE OF CENTRAL ABDO PAIN
Function • Other Sx include wx loss, appetite loss and fever
PANCREAS PROFILE

AMYLASE LIPASE

• Enzyme secreted by • Pancreas enzyme

pancreas and saliva • Secondary Care
• Found in tonsils, small • Highly specific for
bowel, fallopia tubes, Pancreatitis / Pancreatic
thyroid, muscles injury
• Raised in
pancreatitis, thyroidism,
SB injury, vig exercise
John Preddy 02/01/22
 • Thyroid gland is found in the neck & produces thyroxine which modulates metabolism
• TFTs have 3 purposes: Diagnose thyroidism, differentiate from other conditions and
monitor the titration of T4 treatment.
• T4 acts as a negative feedback loop for TSH
• Hypothyroidism = Low T4
THYROID PROFILE
• Symptoms: Decreased metabolic rate, fatigue & weight gain
• Causes: Primary = Hashimoto's / Secondary = trauma, radiation, endometriosis
• Hyperthyroidism = Raised T4
• Symptoms: Increased metabolic rate, agitation & weight loss with goitre
• Causes: Primary = Grave's disease / Secondary = Tumour of pituitary gland

TRH TSH T4 T3

• Thyrotropin- • Thyroid- • Monitors thyroid • Produced from

releasing stimulating function T4
hormone hormone • Acts as negative • Used for early
• Produced by • Produced in feedback to diagnosis of
hypothalamus pituritary gland switch off TRH hyperthyroidism
• Acts on pituitary • Stimulates production = T3 > T4
gland to produce thyroid gland to • Monitors T3
TSH secrete T4 therapy
• Low = Non- • Addresses
thyroid illness like hyperthyroidism
DKA, MI, ICU-pts with low TSH
John Preddy 02/01/22
 • T4 for hypothyroidism
THYROID HORMONES Treatment • Carbimazole for hyperthyroidism or 'block' before
medicating with T4 to 'replace'

• 4 & 6 weeks after initiation of treatment initially

Repeat Bloods • 6 monthly thereafter
• Then annually

Hypothalamus

TRH

Pituitary Gland

TSH

Thyroid

T4
Target tissue
John Preddy 02/01/22
 • PTH is required for Ca and Phos balance
• PTH forms 'feedback loop' with Ca, Phos, Mg & VitD
• Conditions that disrupt the loop cause inappropriate ↑ & ↓ in Ca and PTH
• PTH works in 3 ways to control blood Ca levels:
PARATHYROID PROFILE
• ↑ osteoclast resorption of Ca from bone
• Activates VitD in kidney → ↑ absorption of Ca from intestines
• ↓ excretion of Ca in the urine

• ↓ activity of parathyroid glands

Hyperparathyroidism
• ↓ production of PTH
• 1º: ↑ serum Ca & ↓ serum Phos
• 2º: caused by ↓ serum Ca/VitD & ↑ serum Phos
sometimes by CKD
• Symptoms: Bone pain, osteoporosis, stomach pain,
fatigue, thirst

• ↓ activity of parathyroid glands

• ↓ production of PTH
• ↓ serum Ca & ↑ serum Phos
Hypoparathyroidism • Symptoms: PNS, muscle ache/spasms, fatigue, dry skin,
brittle nails & depression

John Preddy 02/01/22

 • DVT is a clot in a vein, which if dislodges form an embolism that can spread to the heart/lungs.
DEEP VEIN THROMBOSIS • Common causes include raised platelets, post-surgery, inactivity or metabolic syndrome.
• Diagnosis involves: Homans test, Wells Score, D-dimer blood test and US...in that order.
• The higher the Wells score the more likely DVT is present, and more likely D-Dimer will be raised.
• D-dimers (Dd) are fragments of clot, broken down by plasminogen. Indicative of large clots

NORMAL RANGES
>16 yrs: <500 ng/ml
11-16 yrs: 160-390 ng/ml WELLS SCORE
Dd less Anti-Co
High WS
relevant initiated

Bedridden/ Calf
Localised
Major swelling Entire Leg Pitting Paralysis or
Med/Low Unlikely Active Ca Prev DVT Tender
-ve Dd surgery >3cm other swollen
veins
Oedma paresiis
WS DVT >3/12 leg

Med/Low
+ve Dd USS
WS

John Preddy 02/01/22

 • Is a clotting process initiated by tissue damage & augmented by platelets.
• 2 components: Intrinsic (Platelet driven) & Extrinsic (Tissue driven).
• Both components lead to: fibrinogen → fibrin → platelet-fibrin clot complex.
COAGULATION PROFILE
• Platelets → express sticky surface proteins → form clot
• Sticky protein = Von Willebrand's factor (VWF)
• Co-exists with inflammatory response so check: WCC/CRP/Neutrophil/ESR/PV.

Related conditions
• Sickle cell disease (abnormal RBC s)
• Thalassemia (inability to produce Hb)
• Haemophilia (absence of VWF or Leiden V)

INR
• Blood test for clotting speed in warfarin patients
• INR>4 problematic for micro-surgery and injections.
• Marker of fibrinogen production & indirectly liver
function.
• Extrinsic pathway .

aPPT
• Blood test for clotting speed in
• INR>4 problematic for micro-surgery and injections.
• Marker of fibrinogen production & indirectly liver
function.
• Extrinsic pathway .
John Preddy 02/01/22
 ANTI-COAGULANTS
COAGULATION PROFILE

Heparin/Deltaparin/LMWH Warfarin Aspirin/Clopidogrel Alchohol

• Intrinsic pathway.
• Binds and deactivates chemicals
that induce a clot.
• Fast acting (minutes)
• Used for prophylaxis
• Assessed by aPPT
• Supresses livers production of
clotting factors.
• Extrinsic & Slow (5 days to work).
• Assessed by INR
• Instrinsic pathway.
• Converted in liver to pro-drugs &
remain in liver days after oral base
drug ceased.
• Effect Platelets → Suppress Von
Willebrand's factor (VWF) → limit
clot
• Clot suppression lasts 2 weeks
• Assessed by aPPT
• Requires platelet
replacement therapy if on high
doses
• Intrinsic and extrinsic pathway
• Acutely supresses VWF activity →
gets platelets drunk and takes off
sticky clothers
• Augmented by liver dysfunction
• Liver does not produce
fibrinogen → clotting time
increases

John Preddy 02/01/22

 • Cholesterol function:
• Develop cell membranes
• Production of bile (makes fat soluble & absorbs vitamins)
CHOLESTEROL PROFILE
• Production of Vitamin D & Steroids
• Production of Sex Hormones (Progesterone/Oestrogen/Testosterone)
• Fat-soluble
• Transported in water-based blood by Chylomicrons
• 'Lousy' LDL
• 'Happy' HDL
• Cholesterol & b-type natriuretic peptide (BNP) are predictive markers of CHD

TOTAL CHOLESTEROL (<0.5)

LDL HDL
• <3.0 healthy • Transports ChL from arterial
wall to liver & adrenal glands
• Helps reduce ChL levels
• Modulates by inhibiting LDL-
induced inflammation &
platelet aggregation in vascular
Triglycerides
• Fat equivalent of glycogen
• Relationship between ↑ TG
& ↓ HDL
• TG is a CVD risk, as 'type of fat'
more likely to be oxidised&
make vascular wall 'stiff'

John Preddy 02/01/22

 CHOLESTEROL TREATMENTS Reduce LDL
Supress liver Side effect can
enzymes HMG- be muscle/ liver
STATINS production in
CoA reductase & damage &
the liver
Acetyl-CoA hyperglycaemia

STATINS Check Creatine Kinase / LFT / Hyperglycaemia

• Atorvastatin • X10 ULN CK MB (brain) / MM (muscle)
• Raised AST/ ALT/ ALP
• Simvastatin • Glucose acutely, Hb1Ac later
• Pravastatin
Change or withdraw statin
• Fluvastatin • Change 1st line management
• Lovastatin
? Myositis / Rhabdomylosis
• Rosuvastatin
• If pain continues with high CK consider ANA, Anti-jo vs
Myoglobin, Kidney profile
John Preddy 02/01/22
 • LDL is known as 'Lousy' as it is bad.
• HDL is known as 'Happy' as it is good.
CHOLESTEROL ANALOGY
• Total cholesterol is like all the people invited to a party.
• It is all the cholesterol in the blood – good, bad and ugly.
• A helpful marker is the cholesterol ratio – Q-risk 3 system <4
(4:1 / LDL:HDL)
• If you are planning a party, it's just as important to think
about WHO to invite as HOW MANY to invite.
• According to the ratio, every 1 happy person (HDL) will
counter the effect of inviting up to 4 lousy people (LDL)

• Statins are bouncers that reduce the amount lousy (LDL)

people at the party
• The bouncers do this by stopping the bar serving these
people drinks (HMG-CoA / ACetyl-CoA) and kicking them
out of the club (Liver)
John Preddy 02/01/22
 • Neuropathy
Diabetes Insipidus Diabetes Mellitus • Retinopathy
• Erectile dysfunction
• Not linked to • Generic name for • Polyuria (destruction of glomeruli)
excess glucose poor glucose Symptoms • Polydipsia (abnormal thirst)
• Confusion
• Caused by control
DIABETES PROFILE
deficient control • Hyperglycaemia
of anti-diuretic caused by poor • ↑ CV risk: Gluc binds to vasc wall
hormone insulin sensitivity → stiffens vasc wall and oxidises
excess LDL.
• 3 causes: • 2 types: • Diabetic neuropathy: excess Gluc
• Neurogenic (no • Type 1 (Insulin bind to nerve cells → suppress
conduction, induce vascular and
vasopressin not produced) neural retraction.
production in • Type 2 (Insulin • ↑ Infection risk: WBC less able to
brain) reach site.
not recognised • Diabetic retinopathy: excess Gluc
• Nephrogenic by cell binds to retinal cells → changes
(kidney does receptors) their structure, causes blurred/ loss
not respond to Complications of vision.
• Diabetic renal dysfunction: excess
vasopressin) Gluc binds to
• Dipsogenic glomerulus/nephrons → eGFR, ↑
Na+ caused by polyuria/dipsia.
(dysfunctional • Diabetic ketoacidosis: fatty acids
thirst used > glucose → produces ketones,
acidic, lower blood pH.
mechanism in
hypothalamus
suppresses
vasopressin)
John Preddy 02/01/22
 INSULIN MEDIATED STORAGE
↑ Glucose OF GLUCOSE AS GLYCOGEN

• Gluc causes insulin to be

released from beta-cells in
DIABETES PROFILE

pancreas
• Insulin coverts Gluc to
glycogen (glycogenesis)
Glucose in fat • Without Insulin, Gluc
Beta-Cell and liver cells stored in fat and liver
cells
• Glycogen stored in liver
A: Type 2
• In between meals or
(↓ insulin B starvation = ↓ Gluc
response) A • Hepatocytes detect ↓
Gluc and affect glucagon
B: Type 1 Liver • Glycogenolysis converts
(no insulin)
glycogen → glucose
Insulin • Gluconeogenesis converts
non-sugars → glucose

Glucose A Glycogen
John Preddy 02/01/22
 • Ax pt's glucose control at random timepoint
Random
• Used in already diagnosed diabetics
Blood • False +ve following high sugar meal
Glucose
DIABETES PROFILE

• Removes chance of false +ve

Fasted
Blood
Glucose

Oral • Measures insulin response following ACUTE

Glucose glucose load to ax insulin response
Tolerance • Completed fasted, 2x BTs 120 mins apart
• Results > Ref range = ↓ insulin efficacy
Test

• Type of Hb with Gluc attatched

• When Gluc in excess Hb becomes
HbA1c irreversibly glycoslated
• LONG TERM marker of diabetes (>49)

John Preddy 02/01/22

 Kidney function may be affected in both
↑ Gluc
types of diabetes so consider U&Es

DM
DIABETES PROFILE

Na+ Urea
↑HbA1c

K+ Creatinine

↑ DM Complimentary blood tests

Na+ & DI
• ↑ in Pancreatitis =
Amylase
↓ Insulin + ↑ Gluc

• ↑ in DKA with ↓ pH
Ketone Bodies

• Insulin converts Gluc →

LFTs
DM & glycogen in liver
↓ ADH
DI
• Stress response = ↑ Gluc
Catecholamines
John Preddy 02/01/22
 DIABETIC MEDICATION
DIABETES PROFILE

Metformin Sulfonylureas
• Inhibits hepatic Gluc (ide-suffix)
production • ↑ Insulin release in
• ↓ Gluc uptake in gut pancreas
• ↑ Insulin sensitive receptors • ↓ excessive glucagon
• ↑ celluar Gluc uptake release in pancreas
• Requires endogenous insulin • Only effective if beta-cell
activity present

John Preddy 02/01/22

 Smoking
• ↑ RBC in tissue hypoxia from smoking (polycythaemia)
• ↑ ESR
LIFESTYLE PROFILE

• ↑ PV & clot risk

• Plasma cotinine = nicotine marker in active smoker

CVD
• ↑ PV and platelets
• ↓ INR
• ↑ Total cholesterol >5 – LDL>3
• ↑ homocysteine = ↑ arterial stiffness from folate deficiency

Alcohol
• ↑ GGT
• LFT - ↑ bilirubin/ AST / ALP

Diabetes
• ↑ HbA1c
• ↑ Fasting glucose
John Preddy 02/01/22