ANAEMIA (Children: See Paediatrics) deficiency.
Def Any condition where there is Hb (♂ <13.5, ♀<11.5), Iron and TIBC: Serum Fe / TIBC
impaired ability of blood to transport O2 Faecal Occult GI Bleeding? (sensitivity 50-75% in CR )
Some anaemias are associated with abnormal Hbs. OGD / Barium Upper GI Bleeding
Classified according to measurement of RBC size (Mean Endo / Barium Lower GI Bleeding
Corpuscular Volume) Coeliac Tests Serum antigliadin, anti endomysium antibodies,
<76 Microcytic (Small & Pale OR Small & Pink) Duodenal Bx.
>96 Macrocytic (Large & Pink & Oval) Pelvic US In females if indicated
76-96 Normocytic (N but in no) Bone M Rarely needed, but will show absent bone-marrow
SMALL AND PALE: aspiration iron stores
Microcytic: Iron Deficiency- Lack of haem Tx: Transfusion not necessary as long as no angina / HF / Cerebral
Microcytic: Thalassaemia- Lack of globin hypoxia.
LARGE AND PINK: Microcystic Anaemia Hx & Exam If Obvious GI Bleeding
Macrocytic: B12 & Folate Deficiency then Tx underlying cause, Otherwise Inv
Macrocytic: Megaloblastic Oral Iron Replacement Therapy (continued for 2-3 / 52 after Hb
SMALL AND PINK: is N to replenish stores)…Hb should by 0.1-0.2 g/dL/day
Congenital membrane defects Ferrous Sulphate: S/E Nausea, Constipation,
Aquired immune defects Diarrhoea.
ODD SHAPES AND SIZES: Failure to recover usually due to compliance, but also…
Inherited: Sickle Cell, Thalassaemia Blood loss, associated inflammatory disease,
Mechanical Damage: DIC malabsorption, combined deficiency state, another
PP 30% total world population are anaemic (15% iron deficient) cause of hypochromic anaemia.
S&S May be asymptomatic if develops gradually Comp Heart F, Exacerbations of angina
Fatigue, SOB Other THALASSAEMIA: Defect in / globulins
Palpitations Cause Classification: / , depending on which pair of Hb chains is
Headache, Tinnitus synthesised inefficiently. NB: Also rare forms.
Unusual dietary cravings (pica) and taste disturbance. PP: Distribution: Throughout S. Europe, S. Asia as well as
Pallor outskirts of Africa. > Common for same reasons as Sickle Cell
Jaundice (Macrocytic- if RBC degradation) vs Malaria.
Atrophic glossitis & angular cheilosis [mouth soreness] (also Pathophysiology & S&S:
signs of megaloblastic anaemia & riboflavin def respectively Thalassaemia (Autosomal Recessive), there is amount or
Brittle, flaking nails & koilonychia (spoon-shaped nails) in no chains chains Damage of RBC.
chronic cases, esp Iron deficient. Heterozygotes: Asymptomatic with Microcytic
Tachycardia, murmurs, cardiac enlargement, and HF (if severe) anaemia
Homozygotes: Severe anaemia in 1st years of life
MCV Iron TIBC Ferritin (Fine until switch occurs from to chains.).
Iron Deficiency Hepatosplenomegaly. Prone to infection. Fe loading.
AOCD N () /N In Thalassaemia (> Complicated since in N people there are
Chronic Haemolysis 2 chains on chromosome 16), there is amount (+
Haemachromatosis (or N) thalassaemia i.e. one chain lost) or no chains (o
Pregnancy N () N thalassaemia i.e. both chains lost) Production of / chains
Sideroblastic Anaemia N// N Haem bind to / chains & does not bind O2.
Thalassaemia N N N o / o Hb Bart’s Hydrops Syndrome: Stillbirth of
severely oedematous (hydropic) fetus at 25-40/40 or
MICROCYTIC ANAEMIA shortly after birth. Mother also at risk of toxaemia of
Path If RBCs cannot aquire Hb at a normal rate in the bone marrow, pregnancy and portpartum bleeding (hypertrophied
they will undergo more division MCV placenta).
Component parts of the Hb molecule are not fully available. o / + Hb H Disease: Associated with mod –
PP Iron Deficiency: Most common cause in all countries. Most severe haemolytic anaemia.
common cause in LEDC are hookworm infection. o / Normal No S&S. Mild MCV, Mild Hb
Risk Females, Vegetarians ( Iron, Phosphates), NSAIDS anaemia.
Cause IRON DEFICIENCY (Fe essential for haem): + / Normal No S&S. Mild MCV
IRON LOSSES: Tx: Genetic screening of mother and then partner if +ve. CVS
GI Bleeding: Oesophagitis, Oesophageal varices, may ID B Thalassaemia. Tx with blood transfusions and
Hiatus hernia, Peptic ulcer, Inflammatory bowel monitor Hep C status.
disease, Haemorrhoids, Carcinoma: stomach, Tx: Iron loading- Desferrioxamine.
colorectal, Angiodysplasia hereditary haemorrhagic CONGENITAL SIDEROBLASTIC ANAEMIA (Very Rare)
telangiectasia (rare) ANAEMIAS OF CHRONIC DISEASE: See Normocytic Anaemia
Rare: Chronic Haemoptysis, Haematuria MACROCYTIC ANAEMIA
MALABSORBTION 1: MEGALOBLASTIC i.e. Large Bone Marrow Cells due to delay in
Hypochlorhydria (Gastric acid needed to release iron maturation…
from food) Cause Occur when defective DNA synthesis occurs in marrow. (In turn this is
Gastrectomy / Previous gastric Sx (for same reason) caused by B12 +/- folate or indeed a defect in folate metabolism)
Vit B12 is absorbed Ileum, Folate is absorbed Upper
facilitated by Intrinsic Factor GI after conjugation.
Growth / Puberty Proliferating cells degrade
from parietal cells or stomach
Poor diet folate
Pregnancy [daily absorption rate of Fe outside preg is
1mg, inside is 500-1000mg
Extra Daily dietary iron requirements per 24 hours. Most absorption is in Vit B12: See below Folate: See below
duodenum & jejunum.
Male 1 mg Indirect Direct
Adolescence 2-3 mg
Intracellular folate metabolism
Female (reproductive age) 2-3 mg
Pregnancy 3-4 mg
Infancy 1 mg
Inv / MCV: Mean corpuscular volume. MCH: mean cell haemoglobin, Defective DNA synthesis in bone marrow
Dx MCHV: mean cell haemoglobin concentration. TIBC: Total Iron
FBC Hb, MCV, MCH, MCHC
Plasma Ferritin Measure of iron stores. Large red blood cells development with nuclei more immature
: Iron deficiency, Hypothyroidism, Vit C than their cytoplasm
: Liver disease, Acute Phase response.
Total Iron Measure of iron availability.
Binding Ferritin level: (indicator of body-iron Macrocytic (large) red blood cells appear in the circulation. I.E.
Capacity stores). However, ferritin is acute phase MEGALOBLASTIC ANAEMIA
protein, levels may be N / in with nuclei more immature than their cytoplasm
inflammatory / malignant disease despite Fe
WILL WESTON Page 1 of 14
Serum / RBC Only way to differentiate b/w the two.
VIT B12 DEFICIENCY Folate Treat both while waiting. Tx of B12
Serum B12 with folate may Neuro Relapse!
DIETARY: LFTs Bilirubin if Haemolysis / Liver disease
Strict Vegans and breast fed babies of them. TFTs Hypothyroidism
MALABSORBTION GASTRIC: OGD To confirm gastritis and exclude Ca / polyps,
Hypochlorhydria (Gastric acid needed to release B12 which are 2-3 x > common in pts with Pern A
from food). Bone M asp Cellularity. Confirms: Myelodysplasia,
Gastrectomy / Previous gastric Sx (for same reason), Asplastic anaemia, Myeloma, Others.
Pernicious Anaemia Tx Treat both B12 and Folate since results may take time
80% cause of B12 deficiency B12: Hydroxycobalamin for life.
Incidence: 1:10000 in N Eur, Peak age at 60; Folate: Folic acid supplements (NTDs occur by Day 28/40
F>M (1.6:1); More common in Pts with blue should be taken at conception)
eyes, early greying, blood group A, those Comp Vitamin B12 Neuropathy: Symmetrical damage to peripheral
with FHx or FHx of assoc conditions: Vitiligo, nerves and posterior & lateral columns of spinal nerve with the
Myxoedema, Hashimoto’s disease, legs > affected than arms. Assoc Psychiatric and visual
Addison’s, Hypoparathyroidism] disturbance. M>F. May occur in absence of anaemia.
Autoimmune gastritis Gastric Mucosa Neural tube defects: Folic acid supplements in NTDs
Atrophy levels of intrinsic factor Vit (Spina bifida, Encephalocoele, Anencephaly) in the fetus. May
B12 malabsorption. also Cleft palate and hair lip.
Congenital intrinsic factor deficiency. Gonadal dysfunction: B12 / Folate may Sterility, which is
MALABSORPTION- INTESTINAL: reversible with respective supplementation.
Crohn’s Epithelial Cell : Glossitis and other epithelias surfaces may
Ileal resection. show cytological abnormalities.
FOLATE DEFICIENCY (Body stores sufficient for only ~ 4 months) CV Disease: Assoc b/w folate and MI.
DIETARY: NORMOCYTIC ANAEMIA
Inadequate dietary intake (vegetables). Cause ANAEMIA OF CHRONIC DISEASE:
MALABSORPTION- INTESTINAL: Occurs in: The Big Three (comprising 75%):
Coeliac Disease Chronic Infection / inflammation / Neoplasia
Jejunal Resection Not related to: Bleeding, haemolysis, marrow infiltration.
INCREASED CELL TURNOVER: Pathology: Abnormalities in iron metabolism / erthropoesis.
Pregnancy (esp twins) [also some given to fetus] May Be Normochromic normocytic (More common)
Prematurity May Be Hypochromic microcytic especially when more severe.
Chronic haemolytic anaemia (e.g. Sickle Cell- see Asoc with Crohn’s, RA.Also…
below) Renal disease ( production of erythropoeitin)
Other haemolytic Anaemias: See Normocytic Hypometabolic states (hypothyroidism)
Extensive Inflammatory / Malignant disease. Marrow Damage
RENAL LOSS Bone marrow aspiration may be only way to differentiate b/t
Congestive Cardiac Failure AOCD and Iron deficient.
Dialysis RENAL FAILURE: Erythropoesis
DRUGS HYPOTHYROIDISM (or MCV)
Anticonvusants, Sulphsalazine (Cytotoxic) BONE MARROW FAILURE (Inc APLASTIC ANAEMIA): See below.
…HAEMOLYTIC ANAEMIAS: INC SICKLE CELL ANAEMIA HAEMOLYSIS (or MCV)
Pathophysiology: Sickle Cell etc….See Macrocytic
N: Embryonic Hb HbF at 12/40 HbA after birth. Blood transfusion mismatch
Sickle cell mutation Single aa substitution in B chain See Haemolytic anaemia of newborn
Genetics! Autosomal Recessive. Abnormal erythrocyte fragility
Heterozygotes (Hb SA) have 60% Beta A globin chains and PREGNANCY
40% Beta S chains. Inv / FBC Hb: - Mild anaemia (8.5-11.5)
Homozygotes (Hb SS) have mainly Beta S with small amounts Dx MCV: Normocytic, Normochromic, but up to
of Hb F chains. 25% may be Microcytic. If MCV, then
Amino acid substitution red cell sickling during difficult to distinguish from Iron deficient.
deoxygenation Gels at PO2 agglutination in Serum Iron (but iron stores are N / )
microcirculation, O2 carrying capacity; Blocking of vessels - Tx Treat cause
Anaemia and tissue infarction.
PP: Widespread through Africa as well as immigrant BONE MARROW FAILURE
populations. Some Mediterranians, Middle East, parts of India. Def BMF if the failure of the marrow to produce sufficient
S&S- For Homozygotes (Heterozygotes have no S&S): Red cells + White cells + Platelets
Anaemia; Variable haemolysis; Intermittent crises (bone pain,
worsening anaemia, pulmonary neurological disease). Aka Anaemia + Leucopenia + Thrombocytopenia
Inv: FBC, Hx-Racial origin, Bilirubin, Sickle Cell Test, Hb ALL THREE = PANCYTOPENIA
Electrophoresis (Distinguishes variants…SS, AS etc) The marrow may be:
Tx: Screen pregnant ♀ and Tx babies with penicillin against HYPOPLASTIC or APLASTIC with a in
Strep Pneumoniae, H. Influenzae, N. Meningitidis. haemopoetic cells and in fat spaces.
Tx: Crises: Hydration, Analgesia, Xmatch, O2, ABx. Blood C, REPLACED by abnormal cells / malignant cells that
Reticulocytes, MSU, CXR. Measure organomegaly daily. have arisen in the marrow (1o) or infiltrated (2o).
Tx: Chronic: Hydroxycarbamide. Blood Transfusions. Marrow T. S&S S&S of Anaemia, Infections, Easy bruising / bleeding.
Comp & Tx: Hand & Foot syndrome (Hydration, Paracetamol); Inv Anaemia, Leucopenia, Thrombocytopenia.
Chronic leg ulcers; Gall stones, Osteomyelitis.
DDx Pancytopenia also caused by:
2: NONMEGALOBLASTIC i.e. Normal Bone Marrow Cell maturation Accelerated destruction of cells: Splenomegaly, Autoimmune
Cause Alcohol: Most common cause of Macrocytic anaemia. destruction
SIMILAR DEFECT OF CELL DIVISION (Cells undergo < divisions. Pooling of Cells: Within an enlarged spleen.
Red cell membrane composed of lipid bilayer which is freely Cause 1o In Haemopoeitic Cells (SEE BELOW)
exchanged with plasma lipid.) with: Aplastic Anaemia
Cytotoxic drugs e.g. Hydroxycarbamide Ineffective Haemopoesis
Haematological disease of marrow e.g. myelodysplasia.
Myelodysplasia, Megaloblastic Anaemia
Replacement of Marrow: 1o (SEE BELOW)
Red Cell Aplasia
Leukaemia, Myleoma, Lymphoma
CONDITIONS WHICH LIPIDS depotit on RBC membrane Replacement of Marrow: 2o
MCV [RBCs may have been previously normal] are:
Liver disease (especially associated with OH)
Infiltration by Abnormal Tissue
Myelofibrosis. Rare: Gaucher’s Disease, Amyloidosis,
Inv / FBC Hb, MCV, Platelets, WCC
Dx Serum Iron
Def Chronic pancytopenia assoc with hypoplasic bone marrow.
Fat cell spaces, Bone marrow stem cells
(>75:25%), with no evidence of malignancy.
Plasma LDH , often markedly
Cause Congenital: Autosomal Recessive.
WILL WESTON Page 2 of 14
Acquired: Viral infection (Viral hepatitis, TB) / Radiation / Drug N/V may be severe prescribed with antiemetics.
exposure (ChemoTx). In ½ cause is unknown. Cancer! Particularly acute leukaemia presenting years after Tx
PP Any age, Either sex. Incidence: 2-5 / Million. Drug specific S/E: Eg. Cardiotoxicity with Anthracycines
S&S Rapid / Slow onset. Symptoms: See Bone Marrow Failure. (Doxorubicin).
Liver / Spleen / Lymph nodes: Not enlarged To minimise S/E, ChemoTx given at intervals to allow recovery
Fanconi’s Anaemia: Usually presents in childhood. Assoc of normal cell function b/w cycles
findings: Skeletal and renal tract defects, micrencephaly, RADIOTHERAPY
altered skin pigmentation. In dyskeratosis congenita there are Radiation induces strand breaks in DNA Apoptosis
skin / hair / nail changes. Complications depend on radiosensitivity of N tissue in the path
Inv FBC Normocytic (may be slight macrocytosis) of the radiation field.
Low reticulocyte count. RADIATION S/E:
WCC, Platelets. Lethargy and Energy
Bone Bx 75:25 Fat / Haemopoetic Cell ratio Damage to skin: Erythema, Desquamation
Mx Immunosuppression, Androgens, Bone Marrow Transplant Gut: Nausea, mucosal ulceration, diarrhoea
(severe cases). Testes: Sterility
Comp Bone Marrow: Anaemia, Leucopenia.
Prog Marrow Transplant: 60-70% Cure in younger patients (<20). ALL: ACUTE LYMPHOBLASTIC LEUKAEMIA
PP M>F (Slight). Age: Any but commonly 2-4 yr olds.
REPLACEMENT OF MARROW (PRIMARY) Class T Cell (Peak in adolescent ♂) /B Cell (rare with poor prognosis)
ACUTE CHRONIC S&S Marrow Failure Anaemia, Infection, Bleeding.
LYMPHOID ALL: Acute CLL: Chronic Lymphocytic Leukaemia Also: Bone pain, arthritis, splenomegaly, lymphadenopathy,
(Lymph) Lymphoblastic NHL: Non Hodgkin’s Lymphoma thymic enlargement, CNS involvement (e.g. cranial N palsies)
Leukaemia HL: Hodgkin’s Lymphoma Inv Marrow Bx Characteristic cells in blood & marrow
Multiple Myeloma Mx Supportive: Blood & Platelet transfusions. IV ABx for infection.
MYELOID AML: Acute CML: Chronic Myeloid Leukaemia Chemotherapy.
(WBCs) Myelogenous Myelodysplasia Marrow Transplant: If poor prognosis.
Leukaemia Myeloproliferative Disorders Prog Poor if: Male, Adult, Philadelphia translocation.
Cure for children: 70-90% Cure for adults: 25% (0-20% if > 60)
BLOOD CELL PRODUCTION ACUTE MYELOGENOUS LEUKAEMIA
Lymphomas & Leukaemias are both malignant WBC tumours, but leukaemias PP Incidence: 1:10,000 Per Annum. with age. More common
originate in bone marrow whereas most lymphomas originate in lymph nodes since long term comp for ChemoTx eg for Lymphoma.
Rare in children. Accounts for 80% of all acute leukaemias
Class M1-M7. Morphological Classification (FAB: French, US, British)
S&S 3 Main Areas:
MARROW FAILURE: Anaemia, Infection, Bleeding, DIC
(Diseminated Intravascular Coagulation: Pathological activation
of coagulation mech. Other causes: Infection, Trauma,
Obstetrics. S&S: Extensive bruising, RF, Gangrene)
LEUKAEMIA INFILTRATION: Bone pain, Tender sternum, CNS
S&S (Cord compression, Cranial N Lesions), Gum / Testes /
Orbit (Proptosis), Hepatosplenomegaly, Lymphadenopathy.
CONSTITUTIONAL UPSET: Malaise, Weakness, Fever.
Inv Marrow Bx Differentiation from ALL by microscopy (rods)
Mx Supportive: Blood & Platelet transfusions. IV ABx for infection.
Marrow Transplant: If poor prognosis.
Prog Untreated Death in 2 yrs. Chemotherapy 20% 3 yr survival
CLL: CHRONIC LYMPHOCYTIC LEUKAEMIA
PP 25% of Leukaemias. Usually > 40. M>F (2:1).
Stage 0: Absolute lymphocytosis (>15)
1: Stage 0 + Enlarged lymph nodes
LEUKAEMIA 2: Stage 1 + Enlarged liver / spleen
Def Malignant neoplasms of haemopoetic stem cells, characterised 3: Stage 2 + Anaemia
by diffuse replacement of bone marrow by neoplastic cells. 4: Stage 3 + Platelets
In most cases, cells blood (may be seen in numbers) and S&S None in 25%. Bleeding, Weight , Infection, Anorexia
may infiltrate liver / spleen / lymph nodes / other tissues Enlarged / rubbery / non tender nodes, Late
Acute or chronic disease of that involves blood-forming organs, Hepatosplenomegaly.
characterized by abnormal in no of WBC in tissues +/- Inv FBC etc Lymphocytosis. Hypochromic Microcytic
corresponding of those in circulating blood anaemia. Thrombocytopenia.
Classified according to type of WBC most prominently involved. Mx Chemotherapy: Not usually needed
Class On basis of cell type involved & state of maturity. Radiotherapy: Tx lymphadenopathy / Hepatosplenomegaly
ACUTE: Very immature cells (Blasts) Rapidly fatal in unTx pt Supportive: Transfusions. ABx for infection, Immunoglobulins
ALL: Acute Lymphoblastic Leukaemia Comp Autoimmune haemolysis. Bacterial / Viral infection. B Marrow F.
AML: Acute Myelogenous Leukaemia Prog Often good, but depends on stage. Death is often due to
CHRONIC: More mature leucocytes. infection or transformation aggressive lymphoma.
CLL: Chronic Lymphocytic Leukaemia CML: CHRONIC MYELOID LEUKAEMIA
CML: Chronic Myeloid Leukaemia PP 15% Leukaemias. Most often in middle age with slight M>F.
PP Incidence: 5 / 100 000 Per annum. Path Philadelphia Chromosome ( Apoptosis of Neutrophils): See
Risk GENETIC: above.
> In DS. > In identical twin of affected Pt. S&S Chronic & Insidious: Weight , Tiredness, Gout, Fever,
Philadelphia (Ph) Chromosome found in 95% CML and some Sweats, Bleeding, Abdominal Pain. 10% detected by chance.
ALL pts. Ph = Reciprocal translocation from Chromosome 22 Splenomegaly, Variable hepatomegaly, Anaemia, Bruising.
9, creating an enzyme central to the control of cell proliferation, Inv WCC WCC , FBC /N, Platelets often
apoptosis. Urate & LFTs Urate and ALP
ENVIRONMENTAL: B12 B12
Chemicals: Benzene compounds used in industry Mx Hydroxurea
Drugs: Chemotherapy using chlorambucil & procarbazine Monitor FBC to avoid pancytopenia.
Radiation exposure: Nuclear generators, Tx for Hodgkin’s. Interferon has potential role (Old)
Cause Imotinim (Glivet) is Standard Tx [opposes genetic abnormality
Mx Treatment ChemoTx and RadioTx based (Steroid / Interferon < often). by reversing the P chromosome].
CHEMOTHERAPY: Bone Marrow Transplant (BMT), Stem Cell Transplant (SCT).
Directly damages DNA & RNA, killing cells via apoptosis and Prog Mean survival 3-5 years with old Tx due to eventual transformation to
sometimes necrosis. AML. With BMT and now SCT in young pt = 60% cure.
Affects not only tumour cells, but rapidly dividing N cells of
bone marrow, GI tract, germinal epitherium. LEUKAEMIA COMPARISON TABLE
CHEMOTHERAPY S/E: ALL AML CLL CML
Bone marrow suppression Anaemia, Thrombocytopenia, 80% Child L. 80% Acute Phil Chrmo
Infection. 20% of All L. 30% of All L. 20% of All L.
Mucositis mouth ulceration M:F M>F (Slight) M>F (Slight)
Alopecia Age Children (Also Age > 40s Middle Age
Sterility (may be irreversible) peaks after 50)
WILL WESTON Page 3 of 14
S&S Marrow F (Anaemia, Infection, Bleeding), Nodes, Hep / Splenomegaly STAGE IV Disseminated extralymphatic spread e.g. liver,
Inv Characteristic Marrow. Hb / N Hb bone marrow, skin
Lymphcocytes WCC , Category also placed depending on whether ‘B S&S’ are present.
Platelets /N Platelets
Caegory A: No B Symptoms. Category B = Poor Prognosis
Prog : If M Adult Death in 2 yr if Often good. Depends AML
: Good for No Tx. on Stage. 60% Cure in PP Incidence: 4 / 100,000 / year. M>F (1.5:1)
Children ChmoTx 20% Young Pt. Age: Median 31 years (Peaks at 20-35, 50-70)
3 yr survival Cause Cause unknown. Risk: 3x > common with PMHx Glandular fever, but
no causal link with Epstein Barr virus proven.
Path Spread is contagious from one node to next. Extranodal disease,
such as bone, brain, skin involvement is rare.
DDx Young Pt: INFECTION: EBV / CMV / HIV / toxoplasmosis /
brucellosis; Ongoing regional sepsis: cat scratch disease / TB;
Sarcoidosis; Lymphadenopathy assoc with collagen vascular
diseases; CLL; NHL;
Older Pts: 2 must be included for any localised lymphadenopathy.
Mx STAGES I AND II:
HL Mega-voltage, wide field RadTx (+/- RadTx of adjacent areas)
STAGES III AND IV:
Cyclical combination ChemoTx
Bone marrow transplantation may be useful for selected patients who
have relapsed following treatment with chemotherapy.
Prog Overall, a 5 year survival of >70% should be achieved.
HL Localised disease treated with irradiation there is a 5-year
survival rate of at least 80%.
In disseminated disease treated with cytotoxic chemotherapy
the 5-year survival falls to 50%.
Prognostic indicators include:
AGE - Better prognosis in younger patients
HISTOLOGY - Lymphocytic predominant > Nodular sclerosis >
Mixed cellularity > Lymphocytic depletion
STAGE - Lower has better prognosis
SYMPTOMS - Generalised S&S disease has worst prognosis
NON HODGKIN’S LYMPHOMA
LYMPHOMA Def Malignant tumour of lymphoid tissue.
Def Malignant tumour of lymphoid tissue. Class NON-HODGEKIN’S is divided depending on proliferation rate:
Class Divided clinically & histologically into: Hodgekin’s and Non-Hodgekin’s LOW GRADE:
MAJOR DIFFERENCES BETWEEN THE TWO: E.g. Follicular Lymphoma: 20-30% of NHL
Factor HL NHL Divide slowly, May be present for months before Dx
AGE Bimodal distribution, Many Young. Increase with age. Behave in indolent fashion
Usually have a follicular histology and constitute 30% of the
MODE OF Predicable: Step to step lymph Random
total. 90% of patients are over 50 years old. S&S are often non-
SPREAD nodes starting at neck
specific and disease is usually disseminated at presentation.
HISTOLOGY Polymorphic w diagnostic Reed- Monomorphic, with
Sternberg cells often outnumbered malignant cells most
The intermediate grade accounts for 65% of non-Hodgkin's
by reactive cells, esp eosinophils numerous
lymphoma. Incidence rapidly increasing.
PROGNOSIS 80% potentially curable. Much less. Occur at all ages, with a median age of 65 years.
S&S HL: Lymphadenopathy: painless, rubbery, usually in neck / 2/3 arise in lymph nodes, patient presenting with
supraclavicular fossae. Nodes may be fluctuating in size. lymphadenopathy.
HL: Nodular Sclerosing disease: Young pts may have large Other sites include GI tract, skin and brain.
mediastinal masses (surprisingly asymptomatic, but may dry Most common histological type is large cell B cell lymphoma.
cough, SOB) HIGH GRADE:
HL: Isolated subdiagphragmatic nodes: < 10% at Dx. E.g. Diffuse Large B Cell Lymphoma: 30-40% of NHL
NHL: Lymphadenopathy: Typically disseminated at Divide rapidly, Only present for weeks before Dx
presentation Generalised Painless nodes (In contrast to Rare NHL found primarily in children and young adults.
single nodal group in HL) The main types are:
Visceral lymphadenopathy common, often heavy Lymphoblastic lymphoma
tumour burden but with few symptoms. Burkitt's lymphoma
NHL may also present with anaemia, infections or purpura. May be life threatening
Hepatosplenomegaly. PP AGE: Peak incidence occurs between 50 - 70 years (67% of of
Anaemia cases occur over 60 years). However all ages can be affected
Category B S&S: INCIDENCE: Ages > 15 in UK in 1992: 6,888; No / year / 2000
Fever population was 0.2
Drenching night sweats PREVALENCE: Western Europe & USA NHL account for 55-
Weight loss: >10% in 6/12 60% of all malignant lymphomas. 40% of patients present with
Others: Bone pain, Abdominal Pain, Fatigue, Bruising, tumour outside lymph glands. 1/3 of NHL are Interm – High G.
Generalised itching. Potential Risk: Pesticides, Radiation, HIV (& other reasons for
Inv / FBC May be N. Normochromic normocytic anaemia is bad immunosuppression e.g. Tx of Kidney transplant), EBV,
Dx prognostic factor. Autoimmune disease (e.g. RA, SLE), CLL.
ESR May may raised Mx & LOW GRADE:
Renal F Ensure N prior to Tx Prog Cure is rare. Medial survival is 5-8 years.
Liver F Obstructive pat may be due to Nodes at porta hepatis. Well Pts may not need active Tx but should be reviewed at
LDH Raised levels are adverse prognostic factor regular intervals (e.g. 3-4/12).
CXR May show mediastinal mass Active Tx consists of alkylating agent such as chlorambucil
CT Scan chest, abdo & pelvis to permit staging. Bulky +/- steroids. Remission possible but relapse is inevitable.
disease >10cm in single node mass is prog feature. Occasionally Low Grade Intermediate Grade in which case
Lymph Surgical / Percutaneous needle Bx. aggressive chemotherapy may be successful.
Node Bx INTERMEDIATE GRADE:
Comp Immunosuppression from drugs & disease itself > Infections The tumours are rapidly fatal if not treated.
Tx: CHOP (A combo ChemoTx) +/- radiotherapy
The rate of cure is 40%.
Def Malignant tumour of lymphoid tissue. Curable in 50% with intensive combination chemotherapy.
Class HODGEKIN’S may be staged according to clinical Ann Arbor System Tumour lysis syndrome is frequent problem during ChemoTx
or classified histologically according to the Rye classification. (when tumour cells break down due to Tx, cell contents are
ANN ARBOR SYSTEM released Urea, K+ etc).
STAGE I Involvement of a single lymph node area Chemotherapy tends to work best on faster dividing cells LOW
STAGE II Involvement of 2lymph node regions on same GRADE is not as responsive.
side of diaphragm
STAGE III Involvement of lymph node regions on both sides of
the diaphragm +/- spleen
WILL WESTON Page 4 of 14
cord compression complicating extradural plasmacytomas.
Reduces bone pain and skeletal events. May protect bone and
may cause apoptosis of malignant plasma cells.
Antiangiogenic effects against blood vessels supplying tumours
(also immunomodulatory). Women of childbearing age must
Prog Median survival for pt on standard Tx is 40/12.
< 5% pts survive longer than 10 yrs with standard Tx.
DEHYDRATION (+ FLUID PHYSIOLOGY)
Def State of -ve fluid balance caused by number of disease entities.
PP Diarrhoeal illnesses are most common aetiologies.
Worldwide, dehydration 2 to diarrhoeal illness is leading cause
of infant and child mortality (4 M / Year).
Mortality/Morbidity: Mortality and morbidity generally dependent
upon severity of dehydration and promptness rehydration.
Age: Children < 5 years at highest risk.
BASIC FLUID PHYSIOLOGY:
Average 70 kg pt needs ~ 3 litres day to cover insensible
losses and the necessary intake to maintain N fluid balance.
But: Pts who are physiologically stressed through illness may
have an altered volume / composition of intra / extracellular
spaces as well as kinetics of fluid distribution and excretion.
Increased fluid losses may be due to: Fever, dehydration,
bleeding, or breathlessness.
An extra 500 ml of fluid a day is needed for every degree above
37°C. To preserve plasma volume after trauma, surgery, or in
sepsis, kidney reabsorbs water avidly when stimulated by ADH
(stimulated in turn by pain, anxiety, opioid and anaesthetic
Def Malignant proliferation of plasma cells. agents, and positive pressure ventilation)…may
Primary tumor of bone marrow formed of any one of bone Hyponatraemia esp if only given hypotonic fluids (5% dextrose
marrow cells (as myelocytes or plasma cells). Usually involving or 4% dextrose and 0.18% sodium chloride).
several different bones at same time (Multiple Myeloma) In general, you should aim to give fluid for a reason:
PP Incidence: 4/100,000. M>F (2:1). Median age Dx: 60-70. Maintenance or electrolyte losses:
> Common in Afro Carribeans. Hartmann's solution (avoided in renal & liver failure
Cause because of its K+ and lactate content)
Path Normal: B Cells produce Plasma Cells produce Water losses:
Immunoglobulins (Contain heavy and light chains). Normal Igs 5% dextrose or nasogastric feed
are polyclonal (i.e. variety of heavy chain, each may be of light Expanding intravascular volume:
type kappa / lambda) Blood / Other Colloid
Myeloma Plasma Cells Immunoglobulins (Single heavy and BLEEDING: Acute loss of circulating volume compensatory
Light chain- monoclonal antibody aka paraprotein)
responses. (See- CCC- Shock) Emergency for Mneumonic!) …
Although only small no malignant plasma cells present in
THE FLUID CHALLENGE: Any signs of volume depletion must be Tx
circulation, most present in bone marrow Produce
with a fluid challenge, which is 250 ml of colloid given over 10 minutes
cytokines Osteoclast stimulation Bone resorption
(large bore cannula). Simply maintenance fluid will not help--this
Bone pain, fractures, hypercalcaemia.
will take hours to take effect and during this time, hypoperfusion could
S&S Marrow involvement with malignant plasma cells
cause damage to an organ. Any doubts … Fluid Challenge.
Stimulation of osteoclasts Pain
DIFFERENT TYPES OF FLUID
Pathological fracture Severe local pain
WHOLE BLOOD AND BLOOD PRODUCTS: used in cases of:
Hypercalcaemia Lethargy, thirst
Bone marrow failure Tiredness
Excess production of paraprotein and light chains
Specific problems (e.g. Von Willebrand’s disease) where it is
Renal damage None until uraemic
necessary to provide platelets / clotting factors.
Increased blood viscosity None until severe, then blurred
vision, headache, vertigo, stupor, coma
Substances which do not form true solutions and do not pass
Amyloidosis Nephrotic syndrome
through semi-permeable membranes.
Reduction in no of normal plasma cells
Osmotic potential is so great that draw fluid out of interstitial
Impaired immune function Susceptibility to infection,
and intracellular spaces into plasma, hence often termed
Used in cases of shock where CV function needs improving
Inv / Dx based on two of following: Marrow plasmacytosis, Serum +/- rapidly:
Dx Urinary Paraprotein, Skeletal Lesions
U&Es, Creatinine, Urate Renal Function
Blood Ca, Albumin Presence of hypercalcaemia
WBCs & Platelets usually N
Following haemorrhage, colloids sometimes administered
XR, Blood Alkaline, Presence of bone fractures rather than blood because obtaining blood donor not always
Phosphatase, Isotope bone easy and avoid possibility of a blood transfusion reaction if
scan. cross-matching is not possible or practical.
Plasma Igs Degree of immune paresis Many different types, and all stay in intravascular compartment
FBC, reticulocyte count Degree of bone marrow for varying lengths of time, depending on molecular size.
INR, Coagulation screen Degree of haemostasis Gelatines (Gelofusine and Haemaccel)
Plasma viscosity Blood Viscosity Stay in intravascular compartment 1-2 hours
Serum, B2-microglobulin Disease activity Human albumin
Mx If asymptomatic, treatment may not be required. Stays in intravascular compartment 2-4 hours
High fluid intake for renal impairment & hypercalcaemia. Rarely used because of allergic reactions
Analgesia for bone pain Hydroxyethyl starch
Bisphosphonates for hypercalcaemia Various products with different molecular sizes exist)-some evidence
Allopurinol for nephropathy it capillary leak by unknown mech & stays in intravascular
Plasmapheresis, which may be necessary for hyperviscosity. compartment several hours.
Tx administered until paraprotein levels have stopped falling Substances which form true solutions and pass freely through
(aka the plateau phase). semi-permeable membranes.
Successive relapses respond less well to Tx. Contain water, electrolytes, and sometimes dextrose and stay
RADIOTHERAPY in intravascular compartment < 1 hour.
Effective for localised bone not responding to simple analgesia 5L Crystalloid replace 1 L lost blood (only 1/4 volume stays in
and pathological fractures. Also for emergency Tx of spinal intravascular compartment.
WILL WESTON Page 5 of 14
Hypotonic crystalloids (containing dextrose) should never be Febrile illness: Fever insensible fluid losses and may
used in volume resuscitation. affect appetite.
EXAMPLES: Pharyngitis: This may oral intake.
0.9% Sodium Chloride LIFE THREATENING CAUSES
Contains no K+ Gastroenteritis
So may be given in Hyperkalaemia DKA
Dextrose 5% Burns: Fluid losses may be extreme. Very aggressive fluid
The small amount of glucose, which is quickly management required (see Burns, Thermal).
metabolised, makes the fluid isotonic. Congenital adrenal hyperplasia: May have associated
Used when Oral fluids are prevented. hypoglycemia, hypotension, hyperkalemia, and hyponatremia.
Dextrose 4% And Saline 0.18% GI obstruction: Often assoc with poor intake & emesis. Bowel
Same as above though contains NaCl for urinary ischemia can extensive capillary leak & shock.
losses. Heat stroke: Hyperpyrexia, dry skin, mental status occur.
Ringer’s solution Cystic fibrosis: Excessive Na + Cl losses in sweat, placing pt at
Contains Na , Cl , and some K .
+ - + risk for severe hyponatremic hypochloremic dehydration.
Indicated in water and electrolyte loss when there is Dm insipidus: Excessive output of very dilute urine in large
also some K deficit. Mainly used when severe free water losses & severe hypernatremic dehydration.
vomiting present. (Vomiting H + Cl Metabolic Thyrotoxicosis: Weight is observed, despite appetite.
alkalosis with paradoxical urinary acidosis…Due to Diarrhea occurs.
Renal attempt ot save Na+ since in alkalosis K+ S&S Symptoms
Excretion Then attempt to save K+ H+ Excretion Fluids Freq, Volume, Type (hyper / hypotonic)
Aciduria. Cycle only broken by Fluid & Electolytes) Urine Freq of voiding, Concentrated / dilute, hematuria
Hartmann's Solution (aka Lactated Ringer’s). Stool Freq, consistency, Blood or mucus in stools.
Resembles extracellular fluid since contains Na , K ,
Emesis Freq & Volume (Bilious / nonbilious / hematemesis)
Ca , Cl , and Lactate (which is metabolised to Contact Esp gastroenteritis
bicarbonate…so used to overcome met acidosis). Pmhx CF, Dm, Hyperthyroidism, Renal Disease
COMMON CLINICAL CONDITIONS AND SUGGESTED FLUIDS Other Fever, Appetite patterns, Weight , Travel, Abx use.
Condition + Consequences Need to supply Fluid of choice Signs
DIARRHOEA MILD MODERATE SEVERE
• Water + Electrolytes • Water + Electrolytes Hartmann’s GCS* ALERT LETHARGIC OBTUNDED
• K+ through GI tract • K+ Cap Refill* 2 Secs 2-4 Secs > 4 Secs
• Metabolic acidosis • Bicarbonate/lactate Muc Mems* N Dry Parched, Cracked
SEVERE BLOOD LOSS Tears* N X
• e.g. During Surgery • RBCs + plasma Whole blood Heart Rat Slight Very
VOMITING Resp Rate N + Hyperapnoea
• Water + Electrolytes • Water + Electrolytes 0.9% NaCl or BP N N But Orthostasis
• Metabolic alkalosis Ringers Pulse N Thready Faint / Impalpable
ANOREXIA 0.18% NaCl + Skin turgor N Slow Tenting
• Primary water loss • Water 4% dextrose
Fontanel N Depressed Sunken
U TRACT OBSTRUCTION
Eyes N Sunken V Sunken
• Hyperkalaemia • Water + Electrolytes 0.9% NaCl
Urine output Oliguria Oliguria / Anuria
Path Dehydration often categorized according to serum sodium
* Best indicator for Hydration Status
concentration as one of the below:
DDx Acidosis (Metabolic), Adrenal Insufficiency, Alkalosis, Metabolic, Bowel
Na2+ Hyponatremic (<130 mEq/L) 5-10% Obstruction in the Newborn, Burns, Thermal, Congenital Adrenal Hyperplasia,
Isonatremic (130-150 mEq/L) 80% Dehydration, Diabetes Insipidus, Diabetic Ketoacidosis, Diarrhea, Eating
Hypernatremic (>150 mEq/L) 5-10% Disorder: Anorexia, Enteroviral Infections, Fluid, Electrolyte, and Nutrition
HYPONATREMIC (hypotonic) dehydration occurs when lost Management of the Newborn, Gastroenteritis, Hyperkalemia, Hypernatremia,
Hypochloremic Alkalosis, Hypoglycemia, Hypokalemia, Hyponatremia, Intestinal
fluid contains more sodium than blood (loss of hypertonic fluid). Malrotation, Intestinal Volvulus, Intussusception, Neonatal Sepsis, Oliguria,
Relatively more sodium than water lost. Because serum Pyloric Stenosis, Hypertrophic, Shock, Shock and Hypotension in the Newborn,
sodium is , intravascular water shifts to extravascular Small-Bowel Obstruction
space, exaggerating intravascular volume depletion for given Inv / Na Hyponatremia / Hypernatremia.
amount of total body water loss. Dx K May (eg, congenital adrenal hyperplasia, renal
WARNING: Rapid correction of chronic hyponatremia (>2 failure) or low (eg, pyloric stenosis, alkalosis).
mEq/L/h) has been associated with central pontine myelinolysis Cl May in pyloric stenosis (eg, hypochloremic,
(Stripping of the myelin sheath). hypokalemic, or metabolic alkalosis).
ISONATREMIC (isotonic) dehydration occurs when lost fluid is Bicarb Poor tissue perfusion in dehydration production of
similar in sodium concentration to blood. lactic acid. Bicarb consumed as lactic acid levels . In
Sodium & Water losses are of same relative magnitude in both DKA, ketoacids also consume bicarbonate. Levels can
intravascular and extravascular fluid compartments. also due to loss of bicarb in diarrhoeal stools.
HYPERNATREMIC (hypertonic) dehydration occurs when lost Glucose May be dangerously because of poor intake or
fluid contains less sodium than blood (loss of hypotonic fluid). extremely in DKA.
Relatively less sodium than water lost. Because serum Creat May be because of renal hypoperfusion.
sodium is , extravascular water shifts to intravascular Urinalysis May show findings of DKA (eg, ketones, glucose).
space, minimizing intravascular volume depletion for a given
Tx Estimate fluid deficit. Should be replaced over 4 hours.
amount of total body water loss.
Severity: S&S Infants: weight <10 kg Children: weight >10 kg
WARNING: To compensate for water pulled from cells
Mild 5% or 50 mL/kg 3% or 30 mL/kg
extracellular space, Cells generate osmotically active particles
(idiogenic osmoles) that pull water back Cell. During rapid Moderate 10% or 100 mL/kg 6% or 60 mL/kg
rehydration of hypernatremia, osmotic cell activity can Severe 15% or 150 mL/kg 9% or 90 mL/kg
large influx of water cellular swelling & rupture (cerebral MILD TO MODERATE DEHYDRATION:
Cause -Ve Fluid balance dehydration is due to 1 or more of below: Mild / moderate can usually be Tx very effectively with ORT.
Oral Rehyd Sol CHO Na K Base Osmolality
Output (Renal, Gastrointestinal, Insensible losses),
WHO/UNICEF: 2 90 20 30 310
Fluid shift (ascites, effusions, and capillary leak states
such as burns and sepsis).
Vomiting not CI unless: Evidence of obstruction, ileus, or acute
Decrease in total body water in both Intracellular and
abdomen exists… IV Rehydration indicated.
Extracellular fluid volumes.
Administered in small volumes very frequently to minimize
Clinical manifestations of dehydration are most closely related
gastric distention and reflex vomiting.
to intravascular volume depletion.
5 mL / min is well tolerated. Hourly intake and output should be
As dehydration progresses, hypovolemic shock ultimately
recorded by the caregiver.
ensues, resulting in end organ failure and death.
As child becomes rehydrated, vomiting often decreases and
larger fluid volumes may be used.
Gastroenteritis: Most common cause dehydration. If both
vomiting & diarrhea present, dehydration may progress rapidly.
Stomatitis: Pain may severely limit oral intake.
Lab evaluation and IV rehydration required. Underlying cause
DKA: Dehydration caused by osmotic diuresis. Weight
of dehydration must be determined and Tx appropriately.
caused by both excessive fluid losses & tissue catabolism.
Rapid rehydration, esp rapid initial volume resuscitation, may
PHASE 1: Focuses on emergency management:
poor neurologic outcome. DKA requires very specific and
WILL WESTON Page 6 of 14
Initial Tx includes placement of an IV + rapid administration of Rhabdomyolysis, Tumour Lysis, Large PE
20 mL/kg of lactated Ringer solution or isotonic Haemolysis (eg, venipuncture, blood transf, burns, tumor lysis)
sodium chloride solution. TRANSMEMBRANE SHIFTS (K shift from intra to extracellular space)
Additional fluid boluses may be required depending on Acidosis and medication effects (eg, acute digitalis toxicity,
the severity of the dehydration. beta-blockers, succinylcholine, insulin deficiency)
Frequently reassessed to determine response to Tx. As FACTITIOUS OR PSEUDOHYPERKALEMIA
intravascular volume is replenished, tachycardia, capillary refill, Improper blood collection (eg, ischemic blood draw from
urine output, and mental status all should improve. venipuncture technique), Refridgeration.
If improvement is not observed after 60 mL/kg of fluid Laboratory error, Leukocytosis,Thrombocytosis, Polycythaemia.
administration, other etiologies of shock (eg, cardiac, S&S Hx valuable in ID conditions that predispose to hyperkalemia.
anaphylactic, septic) should be considered. Cardiac and neurologic symptoms predominate.
May be asymptomatic or merely fatigued or…
PHASE 2: Focuses on deficit replacement, maintenance fluids, and Paralysis
replacement of ongoing losses. Palpitations
Less than 10 kg = 100 mL/kg PU Block (Oliguria!)
10-20 kg = 1000 + 50 mL/kg for each kg over 10 kg Poor Tone & Reflexes
Greater than 20 kg = 1500 + 20 mL/kg for each kg over 20 kg Cardiac: Extrasystoles, pauses, bradycardia… See ECG.
Neuro: deep tendon reflexes / motor strength.
Daily maintenance fluid added to fluid deficit. In general, Rare: Muscular paralysis & hypoventilation may be observed.
recommended administration is: Signs of Renal F: Oedema, skin changes, and dialysis sites.
1/2 administered over 8 hours. Signs of trauma: Risk for rhabdomyolysis.
1/2 administration over following 16 hours. DDx Hypocalcemia, Other Problems to be Considered: arrhythmias
Continued losses (eg, emesis, diarrhoea) must be Inv / U&Es Evaluation of renal status
replaced promptly. Dx Calcium If patient has renal failure (because hypocalcemia can
If Isonatremic, sodium deficit incurred can be corrected by exacerbate cardiac rhythm disturbances)
administering fluid deficit + maintenance as … Glucose In patient with diabetes mellitus
5% dextrose in 0.45% NaCl.
Digoxin If patient is on a digitalis medication
Potassium (20 mEq/L KCl) may be added once urine
ABGs If patient is on a digitalis medication
output is established.
Urinalysis If signs of renal insufficiency are present (to look for
If Hyponatraemic, rehydration is calculated as for isonatremic
evidence of glomerulonephritis)
dehydration BUT additional sodium deficit must be calculated
and added to the rehydration fluids.
ECG Early of HK include:
5% dextrose in 0.9% NaCl or 0.45% NaCl as the Peaked T waves
replacement fluid. Sodium is monitored closely, and QT interval
amount of sodium in fluid is adjusted to maintain slow ST depression…
correction (<0.5 mEq/L/h). Followed by bundle branch blocks
If Hypernatraemic, rehydration is calculated as for isonatremic Widened QRS complex
dehydration BUT most important goal is to reestablish PR interval
intravascular volume slowly. Amplitude of P wave.
5% dextrose in 0.9% NaCl. Serum sodium levels Appropriate treatment reversal of ECG .
should be assessed every 4 hours. If the sodium has Without Tx, P wave eventually disappears and
decreased by less than 0.5 mEq/L/h, then sodium QRS morphology widens to resemble a sine
content of the rehydration fluid is decreased. wave. V Fibrillation or asystole follows.
ECG findings generally correlate with K+ level,
ION / SUMMARY OF MAIN CAUSES but life-threatening arrhythmias can occur
HYPER HYPO without warning at almost any level of HK.
K+ Renal Failure Vomiting, Diarrhoea Cortisol, Check for mineralocorticoid deficiency when other
K+ Sparing Diuretics Diuretics Aldosterone causes are eliminated
Potassium Supplements Hyperaldosteronism (e.g. Mx Prehospital Care:
Rhabdomyalysis Conn’s) IV access established + Cardiac monitoring.
Haemolysis Steroids If hypotension or marked QRS widening:
Acidosis Insulin IV bicarbonate, calcium, and insulin given together
Alkalosis with 50% dextrose
Ca2+ Cancer: Mets Acute Pancreatitis Avoid calcium if digoxin toxicity is suspected.
Cancer: Ectopic PTH Vit D Deficiency Emergency Department Care:
Hyperparathyoidism Hypoparathyroidism Continuous ECG + Vitals.
Thyrotoxicosis Pseudo-Hypoparathyroidism ABCs + Prompt evaluation of cardiac status with ECG.
Paget’s Disease Renal Failure DC any K+-sparing drugs / Dietary potassium.
Thiazide Diuretics (Not all patients should receive every medication …mild HK, for
Na+ Diuretics Diuretics example, may need only excretion enhancement.
Renal Failure Renal F ( Na but H2O) DRUG TREATMENT: Stabilizing the myocardium, shifting K+
Dehydration: Diarrhoea, Cardiac Failure from extracellular environment to intracellular compartment,
Vomiting, Excess Sweating Cirrhosis and promoting the renal excretion and GI loss of potassium:
Hyperaldosteronism (e.g. Nephrotic Syndrome CALCIUM Gluconate (Kalcinate): Ca threshold
Conn’s) Too Much IV Fluid Tx potential restoring normal gradient between
Steroid State: Cushing’s Steroid State: Addison’s threshold potential and resting membrane potential,
SIADH, HONK, DKA which is elevated abnormally in hyperkalemia. Onset
of action is <5 min and lasts about 30-60 min. Repeat
HYPERKALAEMIA if no within 5 mins.
Def Potassium > 5.5…Potentially life threatening condition INSULIN & GLUCOSE: facilitates the uptake of
PP 8% Hospitalised patients. M:F (1:1). glucose into the cell, bringing potassium with it.
Path Nearly 98% of potassium is intracellular, with conc Effects occur within first 30 min of administration.
gradient maintained by Na+/K+/ATPase pump (Pump SODIUM BICARBONATE: Increases pH temp K+
controlled by insulin and B2 receptors). shift from the extracellular to intracellular environment.
Small changes in extracellular K+ may profound effects on Onset of action within minutes, lasts approximately
function of cardiovascular & neuromuscular systems. 15-30 min. Monitor blood pH to avoid excess
A balance of GI intake and renal potassium excretion achieves alkalosis.
long-term potassium balance. BETA-AGONISTS: Promote cellular reuptake of K+,
Class 5.5 - 6.0 mEq/L - Mild condition (possibly via the cyclic gAMP receptor cascade, i.e.
6.1 - 7.0 mEq/L - Moderate condition plasma insulin uptake of K+ into cells).
7.0 mEq/L and greater - Severe condition DIURETICS – FURUSEMIDE: K+ loss via kidney.
Cause DECREASED OR IMPAIRED POTASSIUM EXCRETION: Consultations: Nephrologist / dialysis team for patients with either
Acute or chronic renal failure (most common) severe symptomatic hyperkalemia / Renal F. Admit patients to ICU.
Potassium-sparing diuretics, NSAIDS, Cyclosporins. Prog 1o cause of morbidity & death is K effect on cardiac function.
Urinary obstruction (Bilateral) Mortality can be as high as 67% if severe HK not Tx rapidly.
Sickle cell disease, Addison disease, SLE
ADDITIONS OF POTASSIUM INTO EXTRACELLULAR SPACE HYPOKALAEMIA
Potassium supplements (eg, PO/IV K+, salt substitutes) Def Potassium level less than 3.5 mEq/L.
Ingestion of foods high in potassium (eg, bananas, oranges, Hypokalaemia exacerbates Digoxin toxicity.
high-protein diets, tomatoes, salt substitutes) Never give K+ as stat bolus dose!
WILL WESTON Page 7 of 14
PP As many as 20% of hospitalized patients are hypokalemic; only alkalemia binding ionized calcium.
clinically significant in 4-5% of these. PP Fairly common metabolic emergency.
Severe hypokalemia is relatively uncommon. 10 - 20% pts with cancer develop hypercalcemia at some point
Up to 14% of outpatients are mildly hypokalemic, while in their disease.
approximately 80% of patients who are receiving diuretics Primary hyperparathyroidism occurs in 25 / 100,000 community
become hypokalemic. pts and 75 / 100,000 hospitalized. Most common cause of mild
Sex: M=F. Age: Elderly Pts: Diuretic therapy, diarrhoea, and hypercalcemia, which can be treated on an outpatient basis.
chronic laxative abuse. Incidence with age (due to > hyperparathyroidism & )
Path See Hyperkalaemia. K+ essential for transmission of nerve impulses, Sex: F>M. Annual incidence in ♀> 65 years is 250 / 100,000.
contraction of cardiac muscle, maintenance of intracellular tonicity, Elevations in Ca levels related to have no sex predominance.
skeletal and smooth muscles, and maintenance of N renal function. Path Reference range of serum calcium levels is 8.7-10.4 mg/dL,
Class Moderate hypokalemia is a serum level of 2.5-3 mEq/L. with higher levels present in children.
Severe hypokalemia is defined as a level less than 2.5 mEq/L. 40% bound to protein (primarily albumen)
Cause RENAL LOSSES 50% is ionized and is in physiologic active form.
Renal tubular acidosis, Hyperaldosteronism, Magnesium 10% is complexed to anions.
depletion, Leukemia (mechanism uncertain) See CCC: Osteoporosis
GI LOSSES Cause Divided into PTH-mediated and non–PTH-mediated hypercalcemia.
Vomiting or nasogastric suctioning, Diarrhoea, Enemas or PTH-MEDIATED HYPERCALCEMIA: Ca absorption from gut.
laxative use, Ileal loop Primary hyperparathyroidism originally was disease of
MEDICATION EFFECTS "stones, bones, and abdominal groans."
Diuretics (most common cause), Beta-adrenergic agonists, In most primary hyperparathyroidism cases, Ca is caused by
Steroids (Inc Cushings), Theophylline, Aminoglycosides intestinal calcium absorption. This is mediated by the PTH-
TRANSCELLULAR SHIFT induced calcitriol synthesis that enhances calcium absorption.
MALNUTRITION or dietary intake, parenteral nutrition
Hypercalcemia assoc with malignancy: Unlike PTH-mediated
S&S History: May be vague. Constellation of S&S involving GI, renal, MS, hypercalcemia, Ca that results from malignancy generally
cardiac, and nervous systems. Meds should be reviewed to ascertain worsens until Tx. Hypercalcemia caused by malignancy is
whether could hypokalemia. Common S&S include: result of osteoclastic activity from one of below mechanisms.
Palpitations Tumour Mets Release of osteoclastic activating
Skeletal muscle weakness or cramping
Malignant tissue may release PTH-related protein
Constipation, Nausea or vomiting, Abdominal cramping
Polyuria, nocturia, or polydipsia
Granulomatous disorders E.g. Sarcoid: Macrophages (in
Psychosis, delirium, or hallucinations, Depression
large proportion of granulomas) Release Calcitriol Ca
Signs of ileus
Iatrogenic: Ca is known adverse effect of appropriate dosage
Hypotension in some Tx. In other cases, large ingestions must be taken to
Ventricular arrhythmias, Cardiac arrest, Bradycardia or
induce the increase in calcium levels. Record any vitamin use.
tachycardia, Premature atrial or ventricular beats
Other causes of hypercalcemia
Hypoventilation, respiratory distress, Respiratory failure
Neoplasms (nonparathyroid) - Metastasis to the bone from
Lethargy or other mental status changes
breast, multiple myeloma, and hematologic malignancies
Decreased muscle strength, fasciculations, or tetany,
(Breast cancer is one of the most common malignancies
Decreased tendon reflexes
responsible for hypercalcemia.)
Cushingoid appearance (eg, edema)
Nonmetastatic (humoral-induced) - Ovary, kidney, lung, head
DDx Cushing Syndrome, Hypocalcemia, Hypomagnesemia, Medication
and neck, esophagus, cervix, lymphoproliferative disease,
side effect, Renal tubular acidosis
multiple endocrine neoplasia, pheochromocytoma, and
Inv / Bloods Serum potassium level <3.5 mEq/L (3.5 mmol/L) hepatoma
Dx Bicarbonate if longstanding hypernatraemia. Pharmacologic agents - Thiazide, calcium carbonate (antacid),
BUN and creatinine hypervitaminosis D, hypervitaminosis A, lithium, milk-alkali
Glucose, Mg, Ca, and/or phosphorous if coexistent syndrome, and theophylline toxicity
electrolyte disturbances are suspected. Endocrinopathies (nonparathyroid) - Hyperthyroidism, adrenal
Consider digoxin level if the patient is on a digitalis insufficiency, and pheochromocytoma
preparation; hypokalemia can potentiate Familial hypocalciuric hypercalcemia
digitalis-induced arrhythmias. Tertiary hyperparathyroidism - Postrenal transplant and
Consider arterial blood gases (ABG): Alkalosis can initiation of chronic hemodialysis
cause K+ to shift from extracellular to intracellular. Miscellaneous - Immobilization, hypophosphatasia, primary
Imaging CT scan of the adrenal glands is indicated if infantile hyperparathyroidism, AIDS, advanced chronic liver
mineralocorticoid excess is evident (rarely needed disease
emergently). S&S Symptoms depend on underlying cause, time over which it develops,
ECG T- wave flattening or inverted T waves and overall physical health of the patient.
Prominent U wave (after T wave). "Stones, bones, and abdominal groans."
PR Interval Mild elevations in calcium levels usually have few or no
ST segment depression symptoms.
Ventricular arrhythmias (eg, premature ventricular Increased calcium levels may cause the following:
contractions [PVCs], torsade de pointes, VF) Nausea, Vomiting
Atrial arrhythmias (eg, premature atrial contractions Alterations of mental status, Depression
[PACs], atrial fibrillation)
Abdominal or flank pain, Constipation
Mx PREHOSPITAL CARE: Be attentive to the ABCs.
If severely bradycardic or manifesting cardiac arrhythmias,
Weakness and vague muscle/joint aches
appropriate drug Tx or cardiac pacing should be considered.
EMERGENCY DEPARTMENT CARE:
Severe: ECG; IV access, Assess respiratory status. Headache
Potassium replacement Tx according to S&S & K+ level. Coma: If Severe
(Usually, patients who have mild / moderate hypokalemia (K+ Elderly patients are more likely to be symptomatic from
2.5-3.5 mEq/L), are asymptomatic, or have only minor S&S moderate elevations of calcium levels.
need only oral K+. If cardiac arrhythmias or significant S&S Hypercalcemia associated with renal calculi, joint complaints,
present, then > aggressive therapy warranted. This Tx is similar ulcer disease is > likely to be caused by hyperparathyroidism.
to Tx for severe hypokalemia. Hypercalcemia has few physical findings specific to its Dx.
If the K+ <2.5 mEq/L, IV potassium should be given. Often it is S&S of underlying malignancy seek attention.
K+ difficult to replenish if serum Mg also low. Replace both. Primary malignancy may be suggested by lung findings,
CONSULTATIONS: skin , lymphadenopathy, or liver or spleen enlargement.
An internist or a nephrologist should be consulted for admission Hypercalcemia can produce a number of nonspecific findings,
or follow-up care. as follows:
Prog If K+ replaced too quickly, rapid in serum potassium Hypertension and bradycardia may be noted in
level can hyperkalemia; however, the total body reserves patients with hypercalcemia.
of potassium might still be less than normal. Abdominal examination may suggest pancreatitis or
the possibility of an ulcer.
HYPERCALCAEMIA (See Chronic CCC-Osteoporosis for Diagram) Patients with long-standing elevation of serum calcium
Def Hypercalcemic crisis does not have an exact definition, may have proximal muscle weakness that is more
although marked of serum Ca, usually > 14 mg/dL, is assoc prominent in the lower extremities; they also may have
with acute S&S of hypercalcemia. Tx of calcium level may bony tenderness to palpation.
resolve the crisis. Hyperreflexia & tongue fasciculations may be present.
Acute acidemia calcium binding to albumin, whereas Anorexia or nausea may occur.
WILL WESTON Page 8 of 14
Polyuria and dehydration are common. hypocalcemic emergencies in the ED and include the following:
Lethargy, stupor, or even coma may be observed. Acute pancreatitis: Free fatty acids chelate calcium,
Long-standing hypercalcemia may cause band keratopathy, but causing saponification in the retroperitoneum.
this is rarely recognized in the ED. Rhabdomyolysis: Increased phosphates from
If hypercalcemia is caused by sarcoidosis, vitamin D creatine phosphokinase (CPK) and other anions (ie,
intoxication, or hyperthyroidism, patients may have physical lactate, bicarbonate) chelate calcium.
examination findings suggestive of those diseases. Sepsis can hypocalcemia.
DDx HIV Infection and AIDS, Hyperparathyroidism, Sarcoidosis, Toxic shock syndrome can hypocalcemia.
Tuberculosis, Toxicity: Lithium / Salicylate / Theophylline / Thyroid High calcitonin levels calcium.
Hormone / Vitamin. Other Problems to be Considered: Malignancy: Osteoblastic metastases (eg, breast
Pheochromocytoma, Immobilization, Addison disease, Inflammatory cancer, prostate cancer) and tumor lysis syndrome
disorders, Rhabdomyolysis, Paget disease, Parenteral nutrition may cause hypocalcemia (by differing mechanisms).
Inv / Lab Confirmatory tests: in serum protein concs Hepatic or renal insufficiency: Calciuresis,
Dx Studies: alter total serum Ca level but do not affect hypomagnesemia, hypoalbuminemia, and active
unbound fraction. Ca reported by lab usually vitamin D levels may poor calcium homeostasis.
represents bound + unbound Ca. When Ca Infiltrative disease: Sarcoidosis, tuberculosis, and
levels reported as or , physician must be hemochromatosis may infiltrate parathyroids,
able to calculate actual level of calcium. dysfunction.
Serum Ca & Phos, U&E, LFTs, PTH, . Toxicologic causes include hydrofluoric acid burn or
Alb, Cl, K, Enhanced protein binding and anion chelation
Alkalosis Protein binding is enhanced by elevated pH and free
Phos, ALP fatty acid release in high catecholamine states.
Ca + Alb + + Urea Dehydration Anion chelation is seen in phosphate states (eg,
Ca + Alb + + N Urea Cuffed Specimen renal failure, rhabdomyolysis, mesenteric ischemia,
Ca + N/Alb + Phos N/ + N Urea 1o / 3o Hyprparathyroidism oral administration of phosphate-containing enemas);
Ca + N/Alb + Phos /N + ALP Bone Mets*, Sarcoidosis, citrate states (eg, massive blood transfusion,
Thyrotoxicosis radiocontrast dyes); and bicarbonate, lactate, and
Ca + N/Alb + Phos /N + N ALP Myeloma, Vit D excess. oxalate levels.
ECG Related to altered trans-membrane potentials Medication effects
that affect conduction time. Calcitonin & bisphosphonates chelation & end-
QT interval shortening (common) organ inhibition.
PR interval is prolonged. Phenobarbital and phenytoin enhance vitamin D
QRS interval may lengthen (Ca) catabolism and calcium resorption in the gut.
T waves may flatten or invert (Ca) Foscarnet complexes with calcium.
Heart block may develop. (Ca) Fluoride, particularly hydrofluoric acid, chelates
Digoxin effects are amplified. (Ca) calcium avidly and causes profound hypocalcemia.
After a Dx of hypercalcemia established, next step is to determine Ethylene glycol complexes with calcium.
cause. Initial testing is directed at malignancy, hyperparathyroidism, Estrogen inhibits bone resorption.
and hyperthyroidism, the most common causes of hypercalcemia. Cimetidine decreases gastric pH, slowing fat
PTH Most direct and sensitive measure of breakdown, which is necessary to complex calcium for
parathyroid function. gut absorption.
Mx PREHOSPITAL CARE: Aluminum and alcohol suppress PTH.
Primarily supportive. If Hx of hypercalcemia & evidence of Gadolinium-based contrast material can falsely lower
acute hypercalcemia, immediately begin IV hydration. serum calcium levels and should be considered if
EMERGENCY DEPARTMENT CARE: levels are drawn shortly after MRI.
Tx depends on level, chronicity, underlying cause of problem. Postsurgical effects
Mild-to-moderate Calcium, few treatment options may be Parathyroid adenoma resection causes a transient
available. A physical evaluation to help delineate source of is hypocalcemia due to end-organ PTH resistance in the
always appropriate, as is a subsequent timely follow-up visit. first postoperative day.
Goals of treatment Vascular/parathyroid injury may occur during trauma
Stabilization and reduction of the calcium level or as an operative mishap.
Adequate hydration Pancreatectomy prevents Ca absorption in duodenum
Severe: Hydration Ca through dilution and the jejunum by eliminating necessary enzymes.
(& extracellular volume Renal Ca Small bowel syndrome hypocalcemia by reducing
clearance) the surface available to absorb fatty acids & calcium.
Hydration ineffective in patients with RF PTH deficiency/resistance
Dialysis. Childhood/congenital causes are rare but include
Increased urinary calcium excretion DiGeorge syndrome.
Loop diuretics (Furosemide) Ca Idiopathic hypoparathyroidism interferes with calcium
Avoid Thiazides ( Ca Absorption) Infiltrative diseases include Wilson disease and
Inhibition of osteoclast activity in the bone metastatic cancer.
Bisphosphanates Pseudohypoparathyroidism is due to PTH resistance
Treatment of the underlying cause (when possible) and has many forms, most notably Albright disease.
Steroids in Sarcoidosis. Renal failure can result in a variety of endocrine
Chemotherapy for malignant disease. disorders, occasionally including hypocalcemia.
Prog Prognosis of hypercalcemia associated with malignancy is poor; 1- Vitamin D deficiency/resistance
year survival rate is 10-30%. In one study, 50% of patients died within Rickets may be due to lack of vitamin D or end-organ
1 month of beginning treatment; 75% died within 3 months. receptor resistance.
Hepatorenal disease: Liver and the kidney provide
HYPOCALCAEMIA intermediary enzymes to form active 1,25(OH)2D.
Def Ca regulation is critical for N cell function, neural transmission, S&S S&S: Muscle cramping, SOB 2o to bronchospasm, tetanic
membrane stability, bone structure, blood coagulation, and contractions, distal extremity numbness, tingling
intracellular signaling. sensations.
PP Frequency: US: Probably > common than hypercalcaemia, but Chronic: Cataracts, dry skin, coarse hair, brittle nails, psoriasis,
less attention. M=F. Age: All ages. chronic pruritus, and poor dentition.
Path See Hypercalcaemia. Acute: Syncope, congestive heart failure (CHF), and angina
Cause Hypoalbuminemia: Most common cause (due to cirrhosis, due to the multiple cardiovascular effects.
nephrosis, malnutrition, burns, chronic illness, sepsis). PMHx: Pancreatitis, anxiety disorders, RF, LF, GI disorders,
Calcium should be corrected in hypoalbuminemic and hyperthyroidism or hyperparathyroidism.
states and often is found to be normal. PSHx: Thyroid, parathyroid, or bowel Sx or recent neck trauma.
Hypomagnesemia: Causes end-organ resistance to PTH and MedHx: Recent radiocontrast, estrogen, loop diuretics,
inhibits hypocalcemic feedback loop through uncertain bisphosphonates, Ca supplements, antibiotics, anti-epileptics.
mechanisms. Causes of hypomagnesemia include Evaluate for appropriate dietary intake.
pancreatitis, aminoglycoside treatment, amphotericin B, loop Neuromuscular and cardiovascular findings predominate.
diuretics, alcoholism, and malnutrition. Neural hyperexcitability due to acute hypocalcemia causes
Hyperphosphatemia: Critical illness, Pt with phosphate- smooth and skeletal muscle contractions. Examine following:
containing enemas. Phosphate binds Ca avidly Acute Ca. Dry skin and psoriasis (if long-term hypocalcemia)
Multifactorial causes are probably the most clinically relevant Perioral anesthesia, cataracts, papilledema, laryngeal stridor
Scars over thyroid region, Recent trauma or surgery to the neck
WILL WESTON Page 9 of 14
Cardiopulmonary effects: HYPERNATRAEMIA DI = Diabetes Insipidus
Wheezing, dysphagia, stridor, bradycardia, rales, and Def Sodium levels tightly controlled in a healthy individual by reg of
S3 may be noted. urine conc and production and reg of thirst response. In
Acute hypocalcemia causes prolongation of the QT patients with intact thirst response, hypernatremia (serum Na
interval, which may lead to ventricular dysrhythmias. It level >145 mEq/L) is a rare entity. When hypernatremia does
also causes decreased myocardial contractility, occur, it is assoc with mortality rate (>50% in most studies).
leading to CHF, hypotension, and angina. In general, hypernatremia can be caused by
Smooth muscle contraction may lead to laryngeal Derangement of thirst response
stridor, dysphagia, and bronchospasm. Derangement of behavioural response thereto
Smooth muscle contraction causes biliary colic, (Infants, psychiatric patients, elderly patients)
intestinal colic, and dysphagia. Problems with renal conc mechanism (Dm insipidus)
Diarrhoea and/or gluten intolerance (celiac sprue) may result in secondary to kidney pathology (nephrogenic DI)
significant malabsorption and electrolyte abnormalities. Difficulty with neurohormonal control of conc
Preterm labour or detrusor dysfunction may result from smooth mechanism (central DI)
muscle contraction. Losses of free water from other sources.
Peripheral nervous system findings include tetany, focal Assessment and Tx Na Pt centres on 2 Important Qs:
numbness, and muscle spasms. What is the patient's volume status?
Classic peripheral neurologic findings include Chvostek sign Is the problem acute or chronic?
and Trousseau sign. PP Frequency: 1% of hospitalized patients esp after admission.
Chvostek sign: Tap over the facial nerve about 2 cm Internationally: Babies in developing nations may be at risk
anterior to the tragus of the ear. Depending on the because infant feeding may be complicated by maternal milk
calcium level, a graded response will occur: twitching production (2o to nutritional status) & errors in reconstitution of
first at the angle of the mouth, then by the nose, the powdered formula.
eye, and the facial muscles. Sex: M=F. Age: Hospital pts tend to be at extremes of age.
Trousseau sign: Inflation of a BP cuff above systolic Breastfed infants occasionally present with hypernatremia in
pressure causes local ulnar and median nerve the first weeks of life, and elderly patients who are
ischemia, resulting in carpal spasm. institutionalized are especially heavily represented.
Irritability, confusion, hallucinations, dementia, extrapyramidal Path Water homeostasis results from balance b/w water intake and
manifestations, and seizures may occur. combined water loss from renal excretion, respiratory, skin, and
Calcification of basal ganglia, cerebellum, and GI sources. Under normal conditions, water intake and losses
cerebrum may occur. are matched. To maintain salt homeostasis, kidneys similarly
Seizures often occur in individuals with preexistent adjust urine conc to match salt intake and loss.
epileptic foci when the excitation threshold is lowered. Hypernatremia results from disequilibrium of one or both of
DDx these balances. Most commonly, disorder is caused by a
Inv / Bloods Ca: Serum Ca < 8.5 mg/dL or an ionized Ca relative free water loss, although it can be caused by salt
Dx <1.0 mmol/L = hypocalcemia. loading.
Falsely levels seen with heparin, Hypernatremia Cells become dehydrated. Shrink.
oxalate, citrate, or hyperbilirubinemia. Cells immediately respond to combat shrinkage & osmotic
Mg, Phos & other electrolyte levels. force by transporting electrolytes across cell membrane
Urea & Creat may indicate renal dysfunction. Rest potentials of electrically active membranes.
Alb, LFTs, Coagulation parameters to assess After an 1 hour: Intracellular organic solutes generated in an
liver dysfunction and hypoalbuminemia. effort to restore cell volume and avoid structural damage. This
The PTH level should be checked ASAP. protective mechanism is important to remember when treating
Imaging Depending on clinical status and suspected a patient with hypernatremia. Cerebral edema ensues if water
etiology of hypocalcemia. replacement proceeds at rate that does not allow for
ECG Dysrhythmias and a prolonged QT interval. excretion or metabolism of accumulated solutes.
Mx Prehospital Care: Effects of cellular dehydration seen principally in CNS, where
Advanced cardiac life support (ACLS) procedures in the patient stretching of shrunken neurons and membrane potentials
whose condition is unstable. No specific therapy, other than ineffective functioning. If shrinkage severe enough, stretching
supportive care, is recommended. and rupture of bridging veins may intracranial hemorrhage.
Emergency Department Care: Hypernatremia is due to too little water, too much salt, or a
The majority of hypocalcemic emergencies are mild and require combination thereof. The alteration can be in administration
only supportive Tx and further laboratory evaluation. On (too much salt or too little water) or output (too much dilute
occasion, severe hypocalcemia seizures, tetany, refractory urine or extrarenal free water losses).
hypotension, or arrhythmias requiring > aggressive approach. Most common cause of hypernatremia in elderly or
Mild hypocalcemia (when symptoms are not life threatening) institutionalized patients is lack of free water intake
Confirm ionized hypocalcemia and check other adequate to meet losses. Thirst is body's main defense against
pertinent laboratory tests. serum tonicity. Most patients with intact thirst mech and
If the cause is not obvious, send for a PTH level. access to water can prevent development of hypernatremia.
Depending on PTH level, endocrinologist may do Even patients with a defective renal conc mech (eg, patients
further lab workup, particularly vitamin D levels. with DI who may produce up to 20 L of urine a day) generally
Oral repletion may be indicated for outpatient can keep up with water losses if allowed free access to water.
treatment; patients requiring intravenous (IV) repletion Some, however, cannot respond to thirst drive. Infants and
should be admitted. elderly patients who are debilitated depend on caregivers to
Severe hypocalcemia (life-threatening symptoms) provide fluids. Similarly, institutionalized patients may have
Supportive Tx often required prior to Tx of Ca (ie, limited access to water secondary to either external or internal
IV, oxygen, monitoring). : Severe hypocalcemia constraints (eg, no access to water in their room, or they
often associated with other life-threatening conditions. believe water is poisoned and refuse to drink it). Intrinsic water
Check ionized Ca and other pertinent screening losses cannot be avoided, and some urine must be produced,
laboratory tests. even if it is max concentrated. Without access to water, these
IV replacement recommended in severe cases. patients encounter a free water deficit, and their serum Na .
In some instances, difficulty stems from an inability of
Ca infusion drips started at 0.5 mg/kg/h and to 2
kidneys to concentrate urine. This is known as DI. DI can
mg/kg/h as needed, with an arterial line placed for
be due to a lack of a central stimulus to concentrate urine (ie,
frequent measurement of ionized calcium.
lack of antidiuretic hormone [ADH] production [central DI]) or
to a lack of renal response to such stimulus (ie, nephrogenic
Depending on the clinical situation, multiple consultations may
DI). The kidneys can fail to respond secondary to resistance to
be necessary, including internist, endocrinologist, intensivist,
vasopressin or due to loss of the medullary-concentrating
surgeon, oncologist, nephrologist, dietitian, and/or toxicologist.
gradient for urine.
Prog Severe, symptomatic hypocalcemia may CV collapse, The differential diagnosis is most easily managed if the
hypotension unresponsive to fluids and vasopressors, and physician considers the patient's volume status…
dysrhythmias. Cause Hypovolemic hypernatremia (ie, water deficit >sodium deficit)
Clinically evident hypocalcemia generally presents in milder Extrarenal losses - Diarrhoea, vomiting, fistulas,
forms and is usually the result of a chronic disease state. significant burns
Chronic or subacute complaints secondary to mild or moderate
Renal losses - Osmotic diuretics, diuretics,
hypocalcemia are more likely to be a chief complaint in the ED
postobstructive diuresis, intrinsic renal disease
than severe symptomatic hypocalcemia.
Adipsic hypernatremia is secondary to decreased
Neurologic sequelae (eg, tetany, seizures) may occur.
thirst. This can be behavioral or, rarely, secondary to
Death is rare but has been reported.
damage to the hypothalamic thirst centers.
Disease causing hypocalcemia may have greater impact on
Hypervolemic hypernatremia (ie, sodium gains >water gains)
morbidity than hypocalcemia itself.
WILL WESTON Page 10 of 14
Sodium bicarbonate administration Mx Emergency Department Care:
Accidental salt ingestion (eg, infant formula error) Mx revolves around 2 tasks: restoration of normal serum
Mineralocorticoid excess (Cushing syndrome) tonicity, and diagnosis and treatment of the underlying
Euvolemic hypernatremia etiology.
Extrarenal losses - Increased insensible loss (eg, When possible, providing free water to a patient orally is
Renal losses - Central DI, nephrogenic DI: Appear Hypernatremia should not be corrected at a rate greater than 1
euvolemic because most of free water loss is from mEq/L per hour.
intracellular and interstitial spaces, with < 10% Carefully monitor all patients' inputs and outputs during
occurring from intravascular space. Typically, S&S treatment.
result if serum sodium is > 160-170 mEq/L. Prog Mortality/Morbidity:
Central DI DDx (deficiency of antidiuretic hormone): Mortality rate is high, esp elderly patients. Mortality rates of 42-
Head trauma 75% reported for acute and 10-60% for chronic. Difficult to be
Suprasellar or intrasellar tumors precise due to comorbidities.
Granulomas (sarcoidosis, Wegener granulomatosis, Morbidity in survivors is high, with many patients experiencing
tuberculosis, syphilis) permanent neurological deficits.
Histocytosis (eosinophilic granuloma)
Acute hypernatremia often significant brain shrinkage
Infectious (encephalitis, meningitis, Guillain-Barré
mechanical traction of cerebral vasculature.
Stretching of bridging veins can in subdural haemorrhages.
Vascular (cerebral aneurysm, thrombosis, Venous congestion can thrombosis of intracranial venous
hemorrhage, Sheehan syndrome) sinuses.
Congenital Arterial stretching can subcortical hemorrhages & cerebral
Transient DI of pregnancy infarctions.
Nephrogenic DI (deficient renal response to ADH) DDx: Seizures possible.
Advanced renal disease (interstitial disease) Hypernatremia of > 2 days' duration is considered chronic
Electrolyte disturbances - Hypokalemia, hypernatremia and assoc with an mortality rate.
hypercalcemia Na > 180 mEq/L often have residual CNS damage.
Systemic diseases - Sickle cell disease, Sjögren If hypernatremia corrected too rapidly, brain edema and assoc
syndrome, amyloidosis, Fanconi syndrome, neurological sequelae can occur. Patients with chronic
sarcoidosis, renal tubular acidosis, light chain hypernatremia are especially prone to this complication.
Dietary disturbances - Excessive water intake, HYPONATRAEMIA
decreased salt intake, decreased protein intake Def BACKGROUND: Serum sodium conc and serum osmolarity normally
Drugs - Lithium, demeclocycline, colchicine, maintained under precise control by homeostatic mechs involving
vinblastine, amphotericin B, gentamicin, furosemide, thirst, ADH, and renal handling of filtered sodium. Clinically significant
angiographic dyes, osmotic diuretics hyponatremia is relatively uncommon and nonspecific in presentation.
Miscellaneous - Postobstructive diuresis, diuretic phase of Total Body Water (TBW), Total Body Na (Na), Extrcllular Fluid (ECF),
acute renal failure, osmotic diuresis, paroxysmal hypertension HYPOVOLEMIC HYPONATREMIA: TBW ; Na+ to a greater
S&S Nonspecific. Anorexia, restlessness, N&V occur early. extent. ECF volume is .
Followed by mental status, lethargy or irritability, and, EUVOLEMIC HYPONATREMIA: TBW while Na remains N. ECF
eventually, stupor or coma. volume minimally to moderately, but edema is not present.
Musculoskeletal symptoms may include twitching, HYPERVOLEMIC HYPONATREMIA: Total body sodium increases,
hyperreflexia, ataxia, or tremor. Neurological symptoms are and TBW increases to a greater extent. The ECF is increased
generally nonfocal (eg, mental status changes, ataxia, seizure), markedly, and edema is present.
but focal deficits such as hemiparesis have been reported. REDISTRIBUTIVE HYPONATREMIA: Water shifts from the
Note signs of volume status, inc mucous membranes, skin intracellular to the extracellular compartment Dilution of Na. TBW
turgor, orthostatic vital signs, and neck veins. and Na are unchanged. This condition occurs with hyperglycemia.
As neurological deficits are common in hypernatremia, perform PSEUDOHYPONATREMIA: Aqueous phase diluted by excessive
a thorough neurological examination. proteins or lipids. TBW and Na are unchanged. This condition is seen
Significant hypovolemia can result when hypotonic fluid losses with hypertriglyceridemia and multiple myeloma.
cause hypernatremia. The physical findings are those of PP Frequency: US: Hyponatremia is most common electrolyte
dehydration or even hypovolemic shock, with tachycardia, disorder, with incidence of 1% of hospitalized patients.
orthostasis, and hypotension. Sex: M=F. Age: Hyponatremia is most common in very young
DDx DI, Salt ingestion, Hypertonic dehydration, Delirium and in very old (less able to experience and express thirst and
Inv / Lab URINE OSMOLARITY: less able to regulate fluid intake autonomously. Specific -risk:
Dx Studies Kidneys response to Na is excretion of a Infants fed tap water in effort to Tx S&S of
minimal amount of max conc urine If urine gastroenteritis
osmolarity , suspect extrarenal hypotonic fluid Elderly patients with diminished sense of thirst, esp
losses. Urine also is concentrated in salt overload when physical infirmity limits independent access to
states, although the total volume should increase. food and drink
Isotonic urine osmolality can be observed with Path
diuretics, osmotic diuresis (mannitol, glucose,
urea), or salt wasting.
Hypotonic urine and polyuria are characteristic of
DI. Note, however, that partial DI can occur in
which some concentrating ability remains,
especially in the absence of a water load.
Na > 190 mEq/L usually indicate long-term salt
Na >170 mEq/L usually indicate DI.
Na: 150-170 mEq/L usually = dehydration.
To ensure osmotic diuresis has not occurred
Imaging Head CT scan or MRI is suggested in all patients with
Studies: severe hypernatremia.
Traction on dural bridging veins and sinuses
caused by movement of water from brain and
brain shrinkage can intracranial hemorrhage,
most often in the subdural space.
Hemoconcentration from total body water loss
may lead to dural sinus thrombosis.
Imaging studies may indicate a central cause for
Other Water deprivation test: With DI, water deprivation
Tests induces serum hyperosmolality and
hypernatremia, but urine osmolality does not
ADH stimulation: With nephrogenic DI, urine
osmolality does not increase after ADH or
desmopressin acetate administration.
WILL WESTON Page 11 of 14
vincristine, SSRIs, sulfonylureas, trazodone, tolbutamide, zalcitabine,
Dehydration, and zonisamide.
Na, Blood Blood
Tx: Saline (+ K supplements)
Diarrhoea & Vomit
Liver Burns, Pancreatitis (Fluid
Juxtaglomerular Extracellular space)
RENIN Cells Sweating (Hyperthermia,
ANGIOTENSINOGEN Addison’s Villous adenoma rectum,
RF Ѕmall bowel obstruction,
Diuretic excess Trauma
Osmolar diuresis ( Glucose, Cystic Fibrosis
ANGIOTENSIN I Urea) Fistula
Na & H2O Lost through kidneys Na & H2O Lost elsewhere
Urinary Na >20mmol/l?
(Also: Relevant to
K Adrenal Cortex ACEi C/I- Dehydrated: YES ( Na )
arterioles > HYPONATRAEMIA
Dehydrated: NO ( H2O)
Is the patient oedematous?
Na + H20 Blood Pressure
CD & DCT Yes: No
Arterial Constriction, Sweating Hydrostatic Pressure Is the urine osmolality
Fluid into Extracellular >500mmol/kg?
space taking Na with it
Anterior Lobe of Serum osmolarity > N Yes No
Pituitary (280-300 mOsm/kg)
Cardic Failure ЅIADH & Other Water overload (or
Liver cirrhosis, inappropriate ADH: Beer)
Osmoreceptors Oliguric Renal Failure Many causes! Dextrose
Thirst (also in Hypothalamus Hypoalbuminaemia, Malignancy, CNЅ, Hypothyroidism,
stimulated by Nephrotic Syndrome Chest, Metabolic, Glucocorticoid
intravascular Drug insuffiency
OH Tx: Saline + H2O Tx: H2O Restriction
Restriction Tx: H2O Restriction
Pain, Stress, Trauma;
S&S Symptoms may be limited to mild anorexia, headache, or
muscle cramps, or patient may present with obtundation,
Healthy kidney regulates Na balance independently of ADH or coma, or status epilepticus.
aldosterone by varying degree of Na absorption at distal tubule. S&S of Cerebral Oedema: Anorexia, N&V, Difficulty
Hypovolemic states, such as haemorrhage or dehydration, prompt concentrating, Confusion, Lethargy, Agitation, Headache,
increases in sodium absorption in the proximal tubule. In vascular Seizures
volume tubular sodium reabsorption, natriuresis and helping to NEUROLOGIC:
restore normal vascular volume. Level of alertness ranging from normal to agitation to
Generally, disorders of sodium balance can be traced to a disturbance in coma
thirst or water acquisition, ADH, aldosterone, or renal sodium transport. Acute Severe: S&S of brainstem herniation:
Hyponatremia is physiologically significant when it indicates a state of Coma; fixed, unilateral, dilated pupil;
extracellular hypo-osmolarity and a tendency for free water to shift from decorticate or decerebrate posturing; and
the vascular space to the intracellular space. Although cellular oedema is respiratory arrest
well tolerated by most tissues, it is not well tolerated within rigid confines In addition to neurologic findings, may be S&S of hypovolemia
of bony calvarium. Therefore, clinical manifestations of hyponatremia or hypervolemia.
are related primarily to cerebral edema. RELATED TO HYPOVOLEMIA:
Rate of development of hyponatremia plays critical role in its Dry mucous membranes, HR, skin turgor,
pathophysiology. When serum Na falls slowly (days / weeks), brain orthostasis
capable of compensating by extrusion of solutes and fluid to extracellular RELATED TO HYPERVOLEMIA:
space. Compensatory extrusion of solutes flow of free water into Pulmonary rales, S3 gallop, peripheral edema, ascites
intracellular space S&S milder for a given degree of hyponatremia. DDx Adrenal Insufficiency and Adrenal Crisis, Congestive Heart Failure
When Na rapidly, (24-48 hours), compensatory mechanism and Pulmonary Edema, Gastroenteritis, Hypothyroidism and
overwhelmed and severe cerebral edema may ensue brainstem Myxedema, Coma, Renal Failure, Acute Renal Failure, Chronic and
herniation death. Dialysis Complications, Syndrome of Inappropriate Antidiuretic
Cause SEE PIC AT END: Hormone Secretion, Other Problems to be Considered: Cirrhosis,
Nephrotic syndrome, Psychogenic polydipsia, Pseudohyponatremia
Hyponatremia can be caused by many medications. Known offenders Iatrogenic, Medication effects
include acetazolamide, amiloride, amphotericin, atovaquone, thiazide Inv / Lab Errors: Tx with glycerol or mannitol in effort to
diuretics, amiodarone, basiliximab, angiotensin II receptor blockers, Dx Studies: control acute glaucoma or intracranial
angiotensin-converting enzyme inhibitors, carbamazepine, hypertension N
carboplatin, carvedilol, celecoxib, cyclophosphamide, clofibrate, Imaging CXR Eg. For CHF.
desmopressin, donepezil, eplerenone, gabapentin, haloperidol, CT: in mental status to rule out other cause.
heparin, hydroxyurea, indomethacin, ketorolac, loop diuretics,
mitoxantrone, nimodipine, oxcarbazepine, opiates, oxytocin,
pimozide, propafenone, proton pump inhibitors, sirolimus, ticlopidine,
WILL WESTON Page 12 of 14
Mx Emergency Department Care: 2 GOALS: To determine (Only temporary- 2-6mins). Reinforced w Fibrin (See Cascade)
chronicity of hyponatremic state and cause. HAEMOSTASIS: STEP 2: DEPOSITION OF FIBRIN
Acute hyponatremia < common than chronic hyponatremia and
typically seen in patients with a Hx of sudden free water loading FIBRINOGEN (Soluble plasma protein) +
(eg, patients with psychogenic polydipsia, infants fed tap water THROMBIN (Protease Enzyme that cleaves fibrinogen)
for 1-2 days, pts given hypotonic fluids in postoperative period).
Ultimate danger for these patients is brainstem Leaving sticky and Insoluble FIBRIN monomers.
herniation when sodium levels fall below 120 mEq/L.
Chronic hyponatremia: Manage with extreme care.
Rapid serum Na once compensatory mechs are In presence of Factor XIII and Ca2+, Monomers Polymerise…
in place can cerebral pontine myelinolysis.
CPM is a poorly understood entity characterized by Stable Clot.
focal demyelination in pons and extrapontine areas.
Symptoms (eg, dysarthria, dysphagia, seizures, Retraction of pseudopodia subsequently Clot to contract to ~40% original
altered mental status, quadriparesis, hypotension) size Tougher + > Elastic + Assists repair (Draws wound edges ().
begin 1-3 days after overly rapid correction of HAEMOSTASIS: STEP 3: VASCULAR CONSTRICTION
serum sodium. Usually result of direct physical damage and mediators released primarily from
The condition is often irreversible; slow, cautious platelets:
correction of serum sodium in these patients is Serotonin
important.: i.e. by 8mmol / day Platelet derived growth factor
Directed at primary cause wherever possible Results from activation of actin-myosin fibrils within endothelial cells, and
NA LOSS: AIM TO REPLACE SODIUM smooth muscle surrounding the damaged vessel.
Healthy pt, oral electrolyte glucose mixture, ↑ salt intake with
slow Na THROMBOSIS PHYSIOLOGY
Vomiting/severe volume depletion, IV normal saline with K+ ACTIVATION OF THROMBIN (Not Normally in Plasma)
supplements Thrombin produced when …Prothrombin activated by Factor X. For this
WATER RETENTION: reaction, Ca2+, Factor V and Phospholipids (PL) are needed.
Restrict fluid intake (to 1000 or even 500ml/day) Two pathways lead to activation of Factor X:
Review of diuretic therapy EXTRINSIC PATHWAY
Correct Mg and K deficiency (potentiate ADH release) Damaged tissues release Thromboplastin (aka Tissue Factor:TF
Hypertonic saline restricted to pts with acute water retention, TF+ Factor VII Directly activates Factor X.
associated with neurological signs Prothrombin (clotting) Time = 14 secs.
Watch for heart failure and central pontine myelinolysis Time if factors V, VII, X deficient
SUMMARY OF ECG CHANGES Takes minutes.
P PR QRS QT ST T Factor XII activated by exposed collagen.
K Small Activated in vitro by –ve charges e.g. glass.
K Cascade follows resulting in activation of Factor X
Ca Requiring Ca2+, and PLs.
Ca Cascading is form of amplification.
Mg SMALL stimulus LARGE amounts of fibrin.
Mg Initial process takes minutes, but subsequent fibrin deposition is
Ischaemia Inversion over in secs. (If blood put in glass, takes 5-10 mins to clot.)
Infarct Inversion Formation of clot all at once is important for haemostasis: (In
Pericarditis haemophilia, clot forms slowly ineffective)
K also Q waves DISSOLUTION OF CLOT AND INHIBITORS OF CLOTTING
A Hyper Gives an increase in most except P Waves and QT Clots destroyed by fibrin breakdown- FIBRINOLYSIS carried out by: Plasmin
A Hypo Gives an decrease in most except P Waves and QT
PLASMINOGEN PLASMIN THROMBOLYSIS
Important that clots do not form inappropriately Antithrombins
CLOTTING CASCADE: Refer to this all the way through! (protease inhibitors) circulate in blood.
Heparin (Derived from mast cells), when combined with antithrombin III is
powerful thrombin inhibitor.
Prostacyclin and NO from endothelium platelet aggregation.
Protein C (activated by thrombomodulin from endothelial cells) with its cofactor
Protein S, inactivates an inhibitor of plasminogen thrombolysis
SUMMARY OF DEFICIENCIES IN HAEMOSTASIS
Haemophilia A Factor VIII
Haemophilia B (Xmas Disease) Factor IX
Von Willebrand’s vWF (Platelet adhesion + transport of VIII)
Disorders of Fat Absorption Vit K (needed in liver for.,.. VII, IX, X
TWO IMPORTANT TESTS…
Prothrombin Measure of activity of extrinsic system in coagulation
Time pathway (II, VII, IX and X).
(PTT) Thromboplastin + Plasma mixed at 37oC
= Time taken for a clot after addition of Ca.
Use of anticoagulants e.g. warfarin
Activated Measure of activity of intrinsic pathway of coagulation (VIII,
Partial IX, XI, XII).
Thromboplastin N Range is 30-45 seconds.
Time Prolonged in:
(APTT) Factor VIII inhibitors
HAEMOSTASIS: STEP 1… Factor VIII / IX / XI deficiency
A) Platelet adhesion, B) Platelet Release Reaction, C) Platelet Aggregation Presence of antiphospholipid antibodies
Damage to vessel wall exposes collagen to blood Heparin usage (Not in LMWH- which is why they are used)
Platelets STICK (A) to collagen Activate RELEASING (B)
HAEMOPHILIA A & B (B: aka Christmas Disease) Sex: M Only
Def Condition 'breeds' true so that in families, all affected members have
SEROTONIN (5HT): ADP::
severe disease or all mild disease. Haemophilia A & B are clinically
Vasoconstrictor Put out Pseudopodia (Sticky)
same and only differ in their cause, frequency and one aspect of Tx.
Flow To Injured Area More Platelets adhere: PLATELET PP A: 1 in 10 000 males B: 1 in 30 000 males.
AGGREGATION (C) (Soft) Class
Rapid Blood Loss Cause A: Congenital deficiency of Factor VIII (VIII:C) coagulant activity.
B: Congenital deficiency of Factor IX coagulant activity.
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Path X-linked recessive disorder (i.e. Males only).
Heterozygous females act as carriers but may be symptomatic
when lyonisation occurs (random inactivation one X in each cell
preferential expression of abnormal X).
Carriers with N levels of factor VIII (40-50%) may show S&S
under severe haemostatic stress e.g. after major trauma.
S&S Bleeding Severity in ‘HP’ related to level of relevant factor. 1 ml
Normal plasma contains 1 unit or 100% Factor activity.
<1% Serious, possibly life-threatening, diasthesis. First S&S is at
about 6 /12 when infant starts to crawl.
<5% Show severe bleeding following injury.
>5% Minor Symptoms
>25% Strictly Haemophiliac but often undiagnosed (Unless Inv)
Bleeding may follow trauma or occurs spontaneously.
HAEMARTHROSES and SOFT TISSUE BLEEDS- Common
If treated inadequately Joint deformity / Crippling.
BLEEDING FROM THE GUT / the RENAL TRACT- Uncommon
CEREBRAL HAEMORRHAGE- Unusual but is most common
cause of death.
Inv / Foetal Prenatal Dx possible in by DNA analysis (CVS). Or:
Dx Levels may be measured from male pregnancies.
Prolong APTT: Depends on Severity (If + Bleed T, DDx: VWD
PT, TCT, Bleeding Time.
Others Specific Factor Assays - differentiate H-A from H-B
DNA Probes: Genes for Factor VIII & Factor IX have been
cloned and characterised.
Pedigree Analysis: Diagnose female carriers with
certainty in some situations – e.g. all daughters of known
haemophiliac male are obligate carriers.
Mx CORRECT THE BLEEDING TENDENCY (Haemophilia A)
IV Factor VIII Concentrate. Most bleeds can be arrested by
plasma level of deficient factor to 30 - 60% of normal.
Cryoprecipitate is another source of Factor VIII.
Mild haemophiliacs may be treated with either / or both:
IV Vasopressin (DDAVP) ( Circulating Factor VIII)
Tranexamic Acid (Antifibrinolytic agent).
CORRECT THE BLEEDING TENDENCY (Haemophilia A)
IV Factor VIII Concentrate. Most bleeds can be arrested by
plasma level of deficient factor to 30 - 60% of normal
Factor IX concentrates contain additional proteins such as
activated coagulating factors ( risk of thrombosis Use
carefully). DDAVP is not effective.
Prompt factor replacement and temporary immobilization of
painful joints are often sufficient to relieve pain.
Analgesics (Paracetamol does not interfere w platelet
function. Not Aspirin! Ibuprofen for chronic pain)
During early painful phase of bleed: Functional Splint, + Active
Exercise (once pain subsided).
Comp Complications Of Treatment
INFECTIONS: Hepatitis B, Hepatitis C, HIV, Parvovirus
ALLERGIES: To other plasma components in cryoprecipitate
Development of anti-Factor VIII antibodies
VON WILLEBRANDS Sex: M=F
PP Type 1: 1% of population; Most common type (70% of VWD).
Type 2: 20-30% of VWD.
Type 3: Extremely rare (one in a million)
Class Three types of von Willebrand's disease are recognised on
basis of ristocetin activity and other tests.
Cause Congenital Deficiency of vWF, a protein cofactor essential for
normal platelet adhesion and for the transport of Factor VIII
Path Inheritance generally autosomal dominant trait with males and
females equally affected.
S&S Severity of bleeding variable. Most are mildly or moderately
affected but some may present like severe haemophilia.
Many asymptomatic and Dx after Perioperative Inv.
Presentation often of mild haemophilia with bleeding following
mild trauma / surgery.
Also: Haemarthroses, soft tissue haematomas, epistaxis and
menorrhagia may occur.
Inv / Bleeding Time, Platelet Adhesion, Factor VIII
Dx Assays of von Willebrand's Factor:
Template bleeding time
Evaluation of vWF protein
Ristocetin Cofactor Activity
Mx Aspirin should be avoided. Treatment depends upon severity.
Replacement Tx advised for patients with severe VWD or
moderate / major surgery.
involves cryoprecipitate infusion / Factor VIII
concentrate of high purity
Cryoprecipitate contains all molecular forms of vWF
and > effective for vWD than factor VIII concentrates.
Alternatives to blood-component Tx include topical thrombin,
Tranexamic acid and DDAVP (synthetic vasopressin).
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