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
                      Menorrhagia
                      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)
                      Coeliac disease
                                                                                                  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
        Binding Capacity
        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
            Aplastic 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:
                                                                                                    Carcinoma
            Liver disease (especially associated with OH)
                                                                                          Infiltration by Abnormal Tissue
            Hypothyroidism
                                                                                                    Myelofibrosis. Rare: Gaucher’s Disease, Amyloidosis,
            Hyperlipidaemia
            Pregnancy
 Inv /   FBC                    Hb, MCV,  Platelets,  WCC
                                                                                 APLASTIC ANAEMIA
 Dx      Serum Iron            
                                                                                 Def       Chronic pancytopenia assoc with hypoplasic bone marrow.
         TIBC                   Saturation
                                                                                                   Fat cell spaces,  Bone marrow stem cells
         Serum Ferritin        
                                                                                                     (>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.
                                                                                                Chemotherapy.
                                                                                                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
                                                                                                  INTERMEDIATE GRADE:
                 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%.
                                                                                                  HIGH GRADE:
 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
                                                                                                 use contraception!
                                                                                  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
                                                                                             Severe haemorrhage
           Bone marrow failure  Tiredness
                                                                                             Severe anaemia
          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
              particular respiratory.
                                                                                                 plasma expanders.
                                                                                             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
                                                                                                         Haemorrhage
         U&Es, Creatinine, Urate              Renal Function
                                                                                                         Shock
         Blood Ca, Albumin                    Presence of hypercalcaemia
                                                                                                         Severe dehydration.
                                              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.
                                                  failure                                EXAMPLES:
         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
           IMMEDIATE:                                                                        Dextrans
            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.
           CHEMOTHERAPY                                                                  CRYSTALLOIDS:
            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)
                                2+   -
                             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
                                                                                                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.
                           Intake
                                                                                                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
            COMMON CAUSES
                                                                                                    larger fluid volumes may be used.
               Gastroenteritis: Most common cause dehydration. If both
                                                                                                SEVERE DEHYDRATION:
                  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
                  controlled treatment.

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
                                                                                                            Paresthesiae
                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
          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.
             Insulin, Alkalosis
                                                                                                NON–PTH-MEDIATED HYPERCALCEMIA:
          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
                                                                                                                 facotors Osteolysis.
             Paralysis, paresthesias
                                                                                                              Malignant tissue may release PTH-related protein 
             Constipation, Nausea or vomiting, Abdominal cramping
                                                                                                                  Ca.
             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.
                                                                                                              Lethargy
             If severely bradycardic or manifesting cardiac arrhythmias,
                                                                                                              Weakness and vague muscle/joint aches
                 appropriate drug Tx or cardiac pacing should be considered.
                                                                                                              Polyuria
             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
                               Malignancy:                                                               ingestion.
                                            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
                                      Excretion                                                           regulation.
                                    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.
                                                                                                         Hypertonic saline

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
                          hyperventilation)                                                          preferred.
                       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.
                          SERUM SODIUM
                           Na > 190 mEq/L usually indicate long-term salt
                           Na >170 mEq/L usually indicate DI.
                           Na: 150-170 mEq/L usually = dehydration.
                          SERUM GLUCOSE
                           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
                               increase appropriately.
                           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
                                  Volume                    Pressure
                                                                                                                                          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
                                                ACE                    Lungs
                                                                                                       Yes:                                         No:
                                                                                              +                                              +
                                                                                            Na & H2O Lost through kidneys                  Na & H2O Lost elsewhere
                       ANGIOTENSIN II
                                                                                                                      Urinary Na >20mmol/l?
                                                      (Also: Relevant to
         K            Adrenal Cortex                      ACEi C/I-                                                 Dehydrated: YES ( Na )
                                                        Constriction of
                                                        efferent renal
                                                          arterioles >                                                  HYPONATRAEMIA
                       ALDOSTERONE                      afferent  
                                                       Renal Perfusion)
                                                                                                                     Dehydrated: NO ( H2O)

                                                                                                                     Is the patient oedematous?
                           Na + H20                   Blood Pressure
                      reabsorbtion (Kidney:
                           CD & DCT                                                                 Yes:                                          No

                                                                                            Hypoosmolarity /
                       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
                           volume)                                                                                                                       (Addison’s: 
                                                                       OH                      Tx: Saline + H2O             Tx: H2O Restriction
                                                                                                  Restriction                                          Tx: H2O Restriction
                                                           Pain, Stress, Trauma;
                                                            Nicotine; Hypoxia
                                                                                       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
                                                                                        Thromboxane A2
          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
                                                                                     INTRINSIC PATHWAY
 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)
 Digoxin Tx                                             
  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.
                                                                                                    Prolonged in:
                                                                                                     Liver disease
                                                                                                     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.
WILL WESTON                                                                                                                                         Page 13 of 14
 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.
                        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.
             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).
             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.
          TREAT PAIN
             Prompt factor replacement and temporary immobilization of
                 painful joints are often sufficient to relieve pain.
             If Inadequate:
                        Joint Asp
                        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).

WILL WESTON                                                                                                      Page 14 of 14

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