Septicaemia

Bacteraemia = "presence of bacteria in blood"

Aet
- N flora - access to bloodstream
eg dental & soft tissue abscesses/cholecystitis/appendicitis/diverticulitis/upper renal tract infection
- **prosthetic surgery (orthop, CVS, neuro) - prosth can be 'seeded' by organism & infect irrev
- Pneumonia - S pneum
- Skin - S pyogenes/S aureus

Sy&Si

Asy (pray that it's not)
or
Severely ill
Fever (absent with child/eld)
Shock (later presentation)
Depressed consciousness (confused/drowsy)
?GN-ve vs G+ve - cannot clinically differentiate

h/e signs poss...
- N meningitidis - purpura
- S Aureus - embolic lesions
- N Gonorrhoeae - arthritis

Dx
x2 peripheral blood cultures b4 Tx
Septic screen
- blood cultures

- urine cult

- sputum cult

- CSF

- skin swabs

- CXR/AXR
- abdo US

Tx
1) empirical DO NOT WAIT!!! - BSp

Empirical Therapies

Skin - strep & staph
-Flucloxacillin
Abdo sepsis - enterobacteriaceae & obligate anerobes
-Ceftazidime & metronidazole/meropenem
Prosthetic devices - staphylococci
-Fluclox/vanc
Urinary Tract - enterobacteriaceae & enterococci
-Piperacillin/tazobactam (init if Hosp acq & sev)
Meninges - N Meningitidis, S pneumoniae, H influenzae
-Benzyl penicillin/Cefotaxime

Line-related septicaemia
- increased risk with time
- S aureus, S epidermidis, Klebsiella
- look for inflammation - remove if susp infection

- Ix - blood cultures from peripherally through cannula
- Tx - ABs, Glycopeptide (MRSA)

- Prevention - ANTT, device w/o dead space/side ports, good dressing, staff hygiene, regular inspection, periph resited every 48hrs, central & tunnelled lines - inspection changed with evidence of infection

- Cx - septicaemia, endocarditis, metastatic infection (eg OMyelitis)

Puerperal Fever
Sev
*bacteraemic infection
Entry of pathogens throo placental bed/cervix following delivery
*w/i 7d of deliv

Sy
Fever
Back pain
Offensive lochia
Shock

Ix

Fever - if in early puerperium = Ix! - bl/ur cult/endocervical swabs

Tx
Empirical
3rd gen cephalosporin & metronidazole
Remove any retained products of contraception
Intensive care if necess

Cx
DIC

Systemic Causes of Haematological Changes #3

Liver Disease

Bleeding
 - deficiency of vitamin K factors (II, VII, IX, X), Factor V, fibrinogen
 - functional abnormalities of fibrinogen
 - increased fibrinolytic activity
 - decreased plts (Hsplen, direct alcohol effect)
 - portal HT - varices

Anaemia
 - bleeding & iron deficiency
 - alcohol - direct toxic effect
 - folate def (megaloblastic An)

 - Hsplen
 - Hlysis - alcohol, Copper (Wilson's), AI (a/w hepatitis)

Red cell changes (macrocytosis, target cells, spur cells)


Chronic Renal Failure

Bleeding

 - abn plt function
 - thrombocytopenia (AI, HUS)

Anaemia
 - decrsd erythropoetin production
 - Fe def (dialysis, venesection, poor plt function)
 - aluminium toxicity
 - folate def (chr dialysis)
 - Hlysis (HUS)
 - anaemia of chronic disease

Red cell changes (Burr cells, fragmented cells in HUS)

Anaemia
 - chronic disease
 - Fe deficiency (Chronic bleeding, *GI tract tumours)
 - immune haemolytic anaemia *NHL
 - pure RC aplasia a/w/ thymoma
 - BM infiltration (extensive)
 - folate deficiency (anorexia, drugs)


Polycythaemia
 - erythropoietin-producing tumours eg kidney, cerebellum, liver

Platelets & coagulation
 - thrombocytosis - eg GI bleeding, reactive
 - DIC - eg mucin-secreting carcinoma
 - coagulation factor aB - eg to factor VIII


Hsplenism
Incrsd pooling, sequestration, destruction

Causes An, Leucop, Tbcytop

Hyposplenism

- splenectomy
- sickle cell dis

- essential thrombocythaemia
- adult coeliac dis

Splenic function impaired by
- corticosteroids
- radiation

Haematological changes
RCCs:
- Target cells

- Howell-Jolly bodies (DNA remnants)

- siderotic granules (iron-containing)

- nucleated RBCs

WCCs:
- early after splenectomy = Nphilia
- ltr = lymphocytosis, monocytosis

Plts:

- early post-splen = marked tbcytosis
- ltr = plts slightly elevated

Cxs:
Increased risk of fulminant infection (*encapsulated bact, malaria)
- S Pneumoniae
- N meningitidis
- H influenzae

Tx

Life-long prophylactic penicillin/erythromycin (prior to splenectomy if poss)
Immunisation - pneumococcus, HiB, meningococcus

Systemic Causes of Haematological Changes #2

Acute Phase Reactants
- general indication of inflammatory resp
eg
Fibrinogen
Complement
CRP
Haptoglobin
Ferritin
Serum amyloid protein

Ix
Presence & extent of inflamation + resp to Tx


ESR
Red cell sedimentation through plasma in 1hr
 - cheap
 - dependant on plasma concentration of large proteins - immglob/fibrinogen
 - raised - chronic infection/myeloma/dissem malig/AI
 - aff by red cell concentration - low in polycythaemia & high in An

Normal range
Men < 5mm/hr
Females < 15mm/hr
Increases with age


Plasma Viscosity
n(1.5-1.7 mPa/s)
15min test
Slight increase with age
Unaffected by red cell changes


CRP
Rapid increase to tiss inj (4-6hrs)
Highly sens
Unaff by RC Changes

?poss - paraproteinaemias

Systemic Causes of Haematological Changes #1

White Cell Changes

Neutrophilia
> 7.5
- Bacterial infection - localised (eg abscess), disseminated (eg septicaemia)
- Inflammation/necrosis - eg MI, vasculitis
- Malignant disease
- Myeloprofilerative disease - eg CML
- Metabolic disease eg uraemia, gout
- Corticosteroid Tx

Leukaemoid reaction
WBC > 50 nt fr leukaemia
Lymphocytes/Neutrophils +/- immature forms
- Severe infections - bacterial eg pneumonia
- Viral - eg infectious mononucleosis
- Severe haemorrhage/haemolysis
- Malignant disease
- Intoxications - eg burns, eclampsia

Ix
BM aspirate/trephine Bp
BM cytogenetics
BM film - Np Granulocytes/Myelocytes
(NB identical to CML, therefore test for Philadelphia chromosone)

Leukoerythroblastic change
Blood shows - nucleated RBCs & primitive WBCs
- Marrow invasion - eg metastatic tumour, Hm malignancy (eg myeloma/lymphoma), fibrosis
- Severe illness - eg trauma, septicaemia, massive haemolysis

Ix
BM trephine biopsy

Neutropenia
< 2
Isolated/pancytopenia

Isolated
- Drugs eg phenylbutazone, co-trimoxazole, carbimazole, anti-psychotics
- Racial
- Congenital eg Kostmann's syndrome, cyclic
- Infections eg hepatitis, typhoid, TB, malaria
- AI eg Felty's, SLE, idiopath

Pancytopenia
- MF - any cause (aplastic anaemia, megaloblastic anaemia, irradiation, malignant infiltration)
- Hypersplenism

Eosinophilia
> 0.5
- Allergies eg asthma, drugs, hayfever
- Parasites eg ankylostoma, ascaris, filaria
- Skin eg eczema, psoriasis, dermatitis herpetiformis
- Malignancy eg Hodgkin's disease
- Inflammatory disease eg sarcoidosis, PAN
- Hypereosinophilic syndrome
- Eosinophilic leukaemia

Hx - for travel, Dx, allerg
Ex - skin, lungs, joints
Ix - as above, stool examination (parasites), RhF, CXR

Lymphocytosis
> 3.5
- Acute infection - *viral eg rubella, mumps, infectious mononucleosis
- Chronic infection - TB, brucellosis, hepatitis
- Thyrotoxicosis
- CLL
- Other Leuks & Lymphomas

Hx - viral illness/night sweats/WL
Ex - throat, LNs, liver, spleen

Viral serology - EBV

Marrow Failure - Myelodysplasia

MDS (myelodysplastic sydromes/myelodysplasia)

Acquired clonal d/o fr haemopoetic stem cells

Epid
Pts *> 70 yrs

Ix & Path
Cytopenias - *An

Morphological evid of dysplasia in blood & BM cells
BM - cellular/Hcellular (NB difference to AA)

Aet
*idiopath
Prev cytotoxic CTx/RTx

Dx
Typical dysplastic changes of Blood & BM
+ Clonal cytogenetic abnormalities on chromosomal examination of BM cells

Prognosis
3 variables
 - % immat blast cells in BM (low blast = best)
 - cytogen abnorms
 - no of cytopenias

Tx

- Supportive - red cell transfusion, iron chelation Tx after multiple transfusions, recombinant erythropoetin therapy
- Cytotoxic CTx - for AML, h/e poor response rate
- Differentiation therapy eg 5-azacytidine (accelerates differentiation of MDS clone, so normal stem cells can regain dominance)
- StC transplantion - definitive cure; only poss 4 small fraction of younger pts

Cx

MDS - *AML

Marrow Failure - Aplastic Anaemia

Features:
- Pancytopenia
- Hypoplastic marrow
- Low reticulocyte count

Si&Sy
Infection/bleeding/anaemia

Causes:
Congenital
Fanconi's (not*)
Acquired
Idiopathic - *AI reaction to BM Stem Cells - eg T suppressor lymphocytes
Radiation - RTx/Occ
Chem - Benzene TNT, DDT
Drugs - Cytotoxic Dx (requires frequent FBCs), other
Viruses

Viral Causes

 - Hepatitis

 - EBV

 - ParvoV

Non-cytotoxic Drug Reactions

 - Chloamphenicol

 - Zidovudine

 - Gold

 - Phenylbutazone

Tx

Remove cause

Supportive - red cell transfusion, ABs, plt transfusion

Stim BM Stem Cells - anabolic steroids

Severe AA
- Np < 0.5
- Plts < 20
- Transfusion-dependant Hb

Tx
BM transplant
- <45yrs
- with HLA matched donor avail
ATG/ALG (anti-thymocyte globulin)
 - removes inhibitory T-cells
 - H/e SE: temp thrombocytopenia & serum sickness
Immsupp
- cyclosporin
- HD steroids

Marrow Failure - Thrombocytopenia

Thrombocytopenia

Decrease in plts prolongs bleeding

(>50 is still okay)
Important to know in case of invasive procedures eg LP

Sy
Purpura/mucosal bleeding

Tx
Plts < 10 = daily transfusion of plt concentrate obtained w/i last 72 hours

Relatives/HLA-matched donors - plt-pheresed on cell separator
Short life-span, so in 24h = x sustained increase in no.

Plt count unreliable mesr of effectiveness

Effective transfusion?
1) Cessation of bleeding
2) Incrs in plt count >20 over baseline, after 1 hr-post transfusion

Problems

HLA aBs in pt (if not matched)

Continued plt consumption at bleeding sites

Marrow Failure - Leucopenia

***Neutrophil count !!!

<1.0 = pyogenic infection
<0.5 = severe risk

FNEs (Febrile Neutropenic Episodes)

Temp = 38.5 x1 or 38x2 w/i 1hr

Ix
Clin exam - severe infection poss from minor inj
Blood M,C&S
Throat sub

MSU

Tx
BSp ABs + change according to sensitivities/if unresponsive to BSpectrum ABs
Continuing fever after ABs = admin of IV anti-fungal agents (amphotericin)

Prophylaxis in Np patients

Barrier Isolation (filtered air & sterile food) = Severely Immunocompromised
Alternatives = Compromise isolation/Home
Compromise isolation = xVisitors with active infections, xFood with bacteria eg cheese, glove & gown

Oral anti-fungals eg nystatin/amphotericin (against oral candida)
x prophylactic ABs except poss LD co-trimoxazole for post-transplant and AIDs pts (against PCP)

Leucocyte Transfusion - from - normal donor treated with G-CSF/pts with chronic granulocytic leukaemia (due to higher no of circulating Nps)


Lymphopenia
Increased risk of viral infections/pneumocystis

Prophylactic aciclovir (against herpes) until T-lymphocyte count > 0.2
Marrow transplant causes immunosuppression * with GVHD
CTx (nucleoside analogues eg fludarabine) also cause immunosuppression

Marrow Failure - Anaemia

Symptoms
Tiredness
Dyspnoea
Angina

Ex
Pale mucous membranes eg eyes

Tx
Transfusion = Packed cells/plasma reduced red cells (NB vol overload)
Adult = 1 unit of blood : 1g/dl in Hb
Aim in-patient = Hb 9-10g/dl
Severe An (Hcrit<.30) = Prolonged BT & can worsen Tbcytopenia

Transfusion reactions
Prev transfusions = antibodies against blood components
eg
- HLA Ag (found on WC & plts)
therefore can = NHFTRs (non-haemolytic febrile transfusion reactions) - from dead WC&Plts in red cells units

Immunocompromised
Require CMV-ve (found dormant in lymphocytes) blood
40% UK donors CMV-ve
Patient CMV aB+ve status useful to establish

Cx
Heart failure

Bone Marrow Failure

Marrow Failure
=
Pancytopenia i.e.
Anaemia
Leucopenia

Thrombocytopenia

2 types

- Hypocellular (empty)

- Infiltrated (competes with normal marrow & normal haemopoetic cells)

Hypocellular
Aplastic Anaemia
Myelodysplasia (can be cellular)
CTx
RTx

Infiltrated
2ry causes (lung/prostate/breast/thyroid/kidney)
Acute leukaemias
Lymphomas
Myeloma

Thrombocytosis

Plts > 500
1ry vs 2ry

1ry
'Essential thrombocythaemia'
Myeloproliferative D/O
Dx of exclusion
25% prolonged BT with abn plt function
25% vascular thromboses (thrombotic and bleeding probs)

Tx
Cytotoxic agents = decreases plt count
(hydroxyurea/radioactive 32P)

2ry
Rarely plt count >1000

Chronic bleeding
Low Fe
Trauma
Inflammation - neoplasm/chronic infection (TB)/Chronic collagen disorders (RA)

Abnormal Platelet Function

Platelets count = normal
BT = prolonged

CFx
Purpura/bleeding mucosa

Aetiology
Congenital
Acquired

Acquired
1) *Drugs (asp/NSAIDS) - NB - stop for 2 weeks and repeat BT
2) Membrane defects (CRF/polycythaemia/raised FDPs)
3) Acquired storage pool disease (myeloproliferative D/Os eg essential thrombocythaemia)

Congenital
Rare
1) Membrane abnormal (Bernard-Soulier Syndrome = deficiency in glycoprotein Ib)
2) Glanzmann's Thromboasthenia (deficiency of gp IIb/IIIa)
3) Arachadonic acid metabolism enzyme defects (cycloxygenase deficiency)
4) Storage Pool Disease (Abn/decreased alpha &/ dense granules)

Ix
i) Plt aggregation studies (ristocetin, ADP, collagen)
ii) ADP & ATP (contents of alpha and dense granules) release post max-stim
iii) Quantify specific membrane protein receptors (*gp Ib & gp IIb/IIIa)
iv) Ix arachadonic acid pathway & Ca flux
v) exclude immunological destruction (plt a/ Ig)

Tx
1) Underlying cause
2) Congenital = plt concentrates (operations/bleeding)
OR DDAVP infusion *storage PD
3) ITP
- Steroids (pred) - suppress immune reaction & inhibit splenic sequestration
- Splenectomy - decrease plt destruction
- HD IV human gammaglobulin (temporary ret-endothelial blockade)
Clinical Course
Post-splen = 60% remission
NB Proph. pneumococc. vacc & long-term penicillin
If splenectomy/steroidx ineffective - other immune suppressants eg azathioprine

Thrombocytopenia

Low Platelet Count

1) Decreased production from bone marrow

2) Peripheral destruction/consumption

- autoimmune (reticuloendothelial system)

- massive clotting process (DIC)

Ix of Choice
Bone marrow examination

Underproduction
1) BM infiltration - leukaemia/secondary malignancy
2) Decrease in megakaryocyte numbers/abnormal differentiation - aplastic anaemia/severe megaloblastic anaemia/excess alcoholism

Peripheral Destruction/Consumption
BM: megakarocytes no. normal or raised

1) Raised peripheral destruction

Pathology
Immunological
aB adh to Plt membranes
Premature ret-end Plt clearance

Aetiology
*ITP (idiopathic thrombocytopenia purpura)
2ry -
SLE
Lymphoid malignancies (B cell chronic lymphocytic leukaemias)
Drugs (quinine, rifampicin)

Ix
Plt a/ Ig (aBs bound to plt surface antigen)

2) Increased consumption

Haemostasis

DIC
Tcytopen assoc with consumption of all clotting Fx
Prolonged coag time
Intravascular haemolytic An
RBCs chopped up by fibrin strands

3) Pooling

1/3 plts pooled in normal spleen
Mod-severe splenomegaly = 'circulating thrombocytopenia'
eg myelofibrosis + mass spleen

4) Massive Transfusion
Bank blood = no functional platelets
Clumps of dead WCCs + plts = microaggregates
Plt adh (before ret-end/lung filtration)
Solution: microaggregate filter in giving set

NB + plt consumption in bleeding site/wound loss

Platelets & Investigations

Platelets
Fragments of megakaryocyte cytoplasm

Megakaryocytes
- giant cells
- multilobulated nuclei
- fr red bone marrow

Platelet Structure
Discus with surface openings on the membrane that connect to the canalicular system
Contains 2 granules
- dense (rich in ADP)
- alpha (contain fibrinogen/factor V, vWF & PA1-1)
and lysosomes
Cytoplasm = Coag Fx - a/w/ the surf membranes

Normal function
BV damage
Plts attach to exposed collagen (underneath endothelial vessel lining)
Plts shape change & degranulate
= ADP release
= activates nearby Plts
Phospholipid released from plts = coagulation system

Defects - can be in no. or function

Tests
Test of number
Electronic particle counters
Blood film

Function test
Bleeding time
 - cuff and cut
Norm <10minutes
New: In-vitro BTs

or

Lab aggregating agents (ADP/collagen) + light transmittance through plasma

Two Basic Initial Tests
1) Plt Count (n = 150-400)
NB if init. low - *artefactual, clot in sample therefore repeat
2) Bleeding Time (n = 2-10 minutes)

The Bleeding Patient

Haemostasis
1) BV constriction
2) Plt adh/activation/aggregation
3) Coagulation factors, leading to a fibrin clot

Bleeding D/Os
2 Types

Platelet Dysf
- superficial bruising
- skin/mucous membrane purpura

Coag Fx Dysfunction
- Deep muscular haemotomas
- Haemarthroses

Causes of Haemolytic Anaemia

SHEEP TIT

ew, but there you go

Sickle cell disease
Hereditary spherocytosis
Enzyme deficiencies (G6PD, pyruvate kinase)
Erythroblastosis fetalis
Paroxysmal nocturnal haemoglobinuria

Trauma to RBCs (mechanical heart valves, DIC, cardiac haemolysis)
Immunohaemolytics (warm Ab, cold Ag, drug induced, transfusion reaction)
Thalassaemias

or TASTE the PuB DISH

Thalassaemia
Autoimmune (warm Ab, cold Ag, drug induced, transfusion reaction, haemolytic disease of the newborn)
Sickling disorders
Trauma to RBCs (mechanical heart valve, cardiac haemolysis, MAHA)
Enzyme deficiencies (G6PD, pyruvate kinase)

the

Paroxysmal nocturnal haemoglobinuria
u
Burns

DIC
Infection (malaria, septicaemia)
Spherocytosis
Hypersplenism

with help from:
http://www.scribd.com/MemorableMedicine

... I really hope that this is relevant...

Otherwise I'd feel like a bit of a tit, making all this effort.
Or a sheep tit, if you will.

Causes of Anaemia

Causes of Microcytic Hypochromic Anaemia

TICS - "Tiny Tics cause Microcytic Anaemia"

Thalassaemia
Iron deficiency
Chronic disease
Sideroblastic anaemia

or "Find Those Small Cells" * - I think this is my favourite

Find = Fe deficiency
Those = Thalassaemia
Small = Sideroblastic anaemia
Cells = Chronic disease.

or "Heavy Sid 's Always after Tha Lasses"

Heavy = Fe = Iron Deficiency
Sid's = Sideroblastic Anaemia
Always = Chronic Disease
Tha Lasses = Thalassaemia


Causes of Normocytic Normochromic Anaemia

ABCD

Acute blood loss
Bone marrow failure/infiltration
Chronic disease
Destruction (haemolytic) anaemia

'nuff said


Causes of Macrocytic Anaemia

"Macdonald's do FAB burgers"

Folate deficiency

Alcohol abuse
B12 (thiamine) deficiency

or

"FAT RBC"

Foetus (pregnancy)
Alcohol
Thyroid (hypo)

Reticulocytosis
B12/Folate
Cirrhosis

or

"FAT RBCs make me MAD"

Foetus (pregnancy)
Alcohol
Thyroid (hypo)

Reticulocytosis
B12/Folate
Cirrhosis

Multiple Myeloma/Myeloproliferative Disorders/Myelodysplasia
Aplastic Anaemia
Drugs (Methotrexate, Zidovudine)

and remember that both B12 and Folate are Megaloblastic, while the rest are Normoblastic.

with help from:
http://www.passmed.co.uk/anaemia.html
http://www.scribd.com/MemorableMedicine