Physiology Flashcards
Two mechanisms by which a metabolic acidosis will occur?
Gain of a strong acid
Loss of a base
How do you figure out anion gap, what is normal?
(Na + K) - (Cl + HCO3)
should be between 10 and 18
Metabolic acidosis - normal anion gap vs raised anion gap causes?
Normal anion gap = hyperchloraemic metabolic acidosis GI loss e.g. vomiting RTA Drugs e.g. acetazolamide Addisons
Raised anion gap:
Lactate - Type A = perfusion e.g. shock, hypoxia, burns.
- Type B = Metabolic e.g. metformin toxicity
Urate raised in renal failure
Acid poisoning e.g. salicylates or methanol
Causes of metabolic alkalosis?
Vomiting Diuretics Hypokalaemia Primary hyperaldosteronism Cushings Barters Syndrome = same as loop diuretics Gittlemans syndrome = same as thiazides CAH
Mechanism of metabolic alkalosis?
Activation of RAAS system is key
Aldosterone causes reabsorption of Na in exchange for H in the DCT
So if ECF depleted = lose Na = more aldosterone = lose H
If hypokalaemia, K shifts extracellular. This means H shifts intracellular to maintain neutrality
Respiratory acidosis cause and examples?
rise in carbon dioxide due to alveolar hypoventilation
Often get metabolic compensation
COPD
Decompensated asthma / CCF
Sedative drugs e.g. benzo’s and opiates
Respiratory alkalosis - mechanism and causes?
Hyperventilation leading to low carbon dioxide
Psychogenic e.g. anxiety
Hypoxia causing subsequent hyperventilation
Early salicylate poisoning
CNS stimulation e.g. strokes, SAH and encephalitis
Vascular changes In acute inflammation?
Inflammatory cells exit at site of injury > disrupts starlings forces > protein rich exudate as cell walls become more permeable
High fibrinogen content may lead to clots
In acute inflammation what are the vasodilators vs vasoconstrictors?
Vasodilators = PGE, histamine, NO, complement C5a and lysosomal compounds
Vasoconstrictor = serotonin. (although in normal tissue it vasodilators)
Sequelae of acute tissue injury?
Resolution = stimulus removed and normal architecture returned
Organisation = delayed removal of exudate, tissue undergoes organisational change and usually fibrosis
Suppuration = forms empyema or abscess > large quantities of dead neutrophils sequester
Chronic inflammation = coupled inflammatory and reparative acts, usually when initial infection poorly managed
What is the histological hallmark of acute inflammation?
Neutrophil polymorphs
Acute vs chronic inflammation?
Acute is usually to existing vasculature, chronic angiogenesis dominates
Acute = neutrophils, chronic = macrophages, plasma cells and lymphocytes
Chronic only heals by fibrosis, acute has the 4 sequelae
What is the cell type of granuloma?
Aggregation of macrophages, with epithelial like arrangement
Large giant cells may be found at the periphery
Mediators of chronic inflammation?
GF’s released by macrophages e.g. IFN and fibroblast GF
Mechanism of necrosis?
Loss of tissue perfusion = hypoxia and cannot generate ATP
Cell membrane integrity lost, lose ATP dependant. transporters
Influx of water, ionic instability + cellular lysis
Release of intracellular contents = inflammatory response
Mechanism of apoptosis?
Programmed cell death
Energy dependent pathways activated by intracellular pathways
Activation of caspases via BCL2 and FAS ligand binding
You get:
- DNA fragments
- Mitochondrial function ceases
- Nuclear and cellular shrinkage
Phagocytosis of cell DOES NOT OCCUR, develop apoptotic bodies
Coagulative necrosis?
Seen in most organs
Tissue initially firm, soft once digested by macrophages
In later stages > cellular outlines seen, with loss of intracellular detail
Colliquative necrosis?
Occurs in tissue with no supporting stroma
Dominant pattern in CNS
Necrotic site eventually becomes encysted
Caseous necrosis?
No definable structure
Amorpheous eosinophilic tissue
Classic in TB
Gangrenous necrosis?
Necrosis with putrefaction of tissue
May complicate ischaemia
Hb degenerates and results in iron sulphide deposition = black tissue
Fibrinoid necrosis?
Seen on arterioles of patients with malignant HTN
Necrosis of smooth muscle walls > plasma may extravasate into media with fibrin
4 phases of wound healing, time frame and cells present at each?
- Haemostasis = seconds to minutes
- vasospasm of vessels and platelet plug formation = generation of fibrin clot
- CELLs = erythrocytes and platelets - Inflammation = days
- Neutrophils migrate = GF’s e.g. VEGF
- fibroblasts replicate
- Macrophages and fibroblasts = matriculates regeneration
- CELLS = macrophages, fibroblasts and neutrophils - Regeneration = weeks
- Platelet derived GF’s
- Fibroblasts form collagen network
- Angiogenesis
- granulation tissue
CELLS = fibroblasts, endothelial cells and macrophages - Remodelling = weeks to year
- Fibroblasts differentiate > myofibroblasts = wound contraction
- micro vessels regress = pale scar
CELLS = myofibroblasts
Scar problems - hypertrophy vs keloid?
Hypertrophy:
Excessive collagen
Nodules = randomly arranged within, parallel on surface
Confined to extent of original wound
Keloid:
Extends beyond original wound
No nodules
Does not regress over time
Drugs impairing wound synthesis?
NSAIDS
Steroids
Anti-cancer drugs
Immunosupressive’s
Secondary closure vs delayed primary?
Delayed primary is waiting a few days after surgery, but before granulation tissue macroscopically visible
Secondary = spontaneous or post-surgery once granulation tissue formed
What is cerebral perfusion pressure?
MAP - intracranial
> 70 is acceptable
MAP equation?
Diastolic + 0.33(systolic - diastolic)
4 types of opioid receptors, where they are found and effect?
Delta = CNS = analgesic an anti-depressant
Kappa = CNS = analgesic + dissociative
Mu. = central and peripheral = analgesia, miosis, decreases gut motility
Nociception receptor = CNS. = appetite and tolerance to Mu receptors
Pain - A fibres vs C fibres?
A =. high intensity mechanical stimulation
C = high intensity mechanothermal stimulation
Neuropraxia vs axonotmesis vs neurotmesis?
Neuropraxia =. nerve intact, electrical conduction affected
Axonotmesis = axon damaged, myelin sheath preserved
Wallerian degeneration
Neurotmesis=. disruption of axon, sheath. and surrounding connective tissue
Wallerian degeneration
Process of wallerian degeneration?
Axonal damage
Myelin sheath degrades and macrophages and Schwann cells infiltrate and clear debris
Schwann cells extrude their own axonal sheath, aligning to form bungner bands and express surface molecules guiding regeneration
Near complete recovery PNS, minimal in CNS (uses oligodendrocytes)
Does intrinsic pathway have major or minor role in clotting, how does it start and which blood test is it?
Minor role
Formation of primary complex on collagen with high molecular weight kininogen + F12
APTT
WEPT?
Extrinsic pathway = main pathway.
- needs tissue factor to be released from damaged tissue = binds to factor 7.
PT
Warfarin = 2, 7, 9, 10
What is the common pathway in clotting?
Factor X to Xa
Xa then with the help of 5a converts prothrombin to thrombin
Thrombin the converts fibrinogen to fibrin = clot
How does clot respiration happen?
Plasminogen converted to plasmin
What factors does heparin affect vs warfarin?
What does lover disease affect?
Warfarin = 2, 7, 9, 10
Heparin = 2, 9, 10, 11
Liver = all except factor 8 as this is made in endothelial cells of the liver = less susceptible to damage
Interpretation of abnormal clotting:
- abnormally raised everything
- raised APTT, bleeding and PT normal
- Raised APTT and bleeding time, PT normal
- Raised APTT and PT, bleeding time Okay
- only raised PT
- DIC
- Haemophilia
- vWD
- Heparin therapy or vitamin k deficiency
- Warfarin
What is the most common inherited bleeding disorder?
vWD
What is vW factors role?
Promotes platelet adhesion to damaged endothelium
Also involved in transport and stabilisation of factor 8
Mx of vWD?
Tranexamic acid for minor procedures
If more severe bleeding can be DDAVP
Stored RBC has lower levels of what?
What is the effect of this?
Lower levels of 2,3-DPG
Means higher affinity to oxygen, so less likely to give it up to metabolising cells
What deficiencies are you at risk of during RBC transfusion?
Factor 5 and 8
As well as thrombocytopaenia
Commonest adverse reaction in RBC transfusion?
Pyrexia
Which blood products can be. ABO. incompatible?
Platelet concentrate and FFP
What is FFP?
Most common adverse reaction of FFP?
Clotting factors, albumin and immunoglobulin
Urticaria
What is in cryoprecipitate?
Factor 8 and fibrinogen
Transfusion reactions:
Immediate
Urticaria, rash + angioedema
Allergic reaction
Recipient IgA deficiency > anti-IgA IgE
Mx = slow transfusion and chlorphenamine
Transfusion reactions:
<6 hours, SOB, cough, raised JVP and leg swelling
Known HF
CCF
slow transfusion, oxygen and furosemide
Transfusion reactions:
<6 hours
SOB + cough, CXR bilateral pleural infiltrates
Pneumonia on admission
TRALI = ARDS
Anti WBC antibodies in donor PLASMA
Mx = stop transfusion and manage ARDS
Transfusion reactions:
Within minutes the patient is agitated, pyrexial and in shock
Massive AKI
Haemolytic reaction
ABO incompatibility
Also get DIC
Mx = stop and treat DIC
Transfusion reactions:
12 hours
Fevers, rigors and shock following platelets
Bacterial contamination
Most commonly seen with platelets
Mx = stop transfusion, Tax and gent
Transfusion reactions:
12 hours after, fever and rigors
non-haemolytic febrile reaction
Recipient anti-HLA antibodies
Mx = slow transfusion + paracetamol
Transfusion reactions:
1 week later, jaundiced anaemic and blood in urine
Delayed haemolytic
Due to recipient anti-Rh antibodies
Extravascular haemolysis
Transfusion reactions:
1 week after transfusion, purpura all over body and low platelets
post-transfusion purpura
Allogenic anti-bodies attack recipient and donor platelets
Mx = IVIG and platelet transfusion
Transfusion reactions:
2 weeks later, diarrhoea rash and jaundiced
GVHD
Due to viable lymphocytes, given in the blood to an immunocompromised patient
Mx = irradiated blood should be given, Mx after is steroid based
Non-immune transfusion reactions?
Low calcium, hyperkalaemia
CCF
infections
How does warfarin work?
Factors it affects?
Things that potentate warfarin?
Inhibits reduction of vitamin K to its active hydroquinone form
2, 7, 9, 10
Liver disease, CYP450 inhibitors e.g. amiodarone and ciprofloxacin, cranberry juice, NSAIDs
Warfarin SE’s?
Haemorrhage
Teratogenic
Skin necrosis
Management of high INR on warfarin?
Major bleeding / urgent reversal for surgery:
Stop warfarin
IV vitamin K
Prothrombin complex (bereplex 50u/kg)
- if no prothrombin complex then cryoprecipitate
INR > 5 with any bleeding: Stop warfarin IV vitamin K 3-5mg Recheck in 6 hours and repeat if still high Start warfarin when INR <5
INR >8 no bleeding: Stop warfarin Oral vitamin K Check ± repeat Restart when INR <5
INR 5-8 no bleeding:
Hold 1-2 doses
reduce subsequent dosing
Heparin:
Mechanism?
why its better than unfractionated?
complications?
Causes formation of complexes between anti-thrombin and activated thrombin
Longer half life, lower risk of HIT, little effect on APTT
Bleeding, osteoporosis, HIT (2 weeks after dosing)
How does tranexamic acid work?
Inhibits conversion of plasminogen to plasmin = plasmin degrades clots
Causes of severe thrombocytopenia?
ITP
DIC
TTP
Haematological malignancy
Causes of moderate thrombocytopenia?
Liver disease and alcohol Hypersplenism Viral infection HIIT Pregnancy B12 deficiency
Mechanism of DIC?
Dysregulation of coagulation and fibrinolysis
Tissue factor gets exposed to general circulation (doesn’t normally happen)
This causes clotting cascade ++
This then uses up all the clotting factors (namely 5 and 8) = bleeding ++
Clinical features of DIC and causes?
bleeding
Cough and SOB and fever
All bleeding parameters raised
Causes = sepsis, malignancy, trauma and liver disease
Antibodies for anti-phospholipid syndrome?
Anti-cardiolipin
Lupus anticoagulant
Criteria for anti-phospholipid syndrome?
Thrombus in any organ, or pregnancy event (1 miscarriage >10 weeks, 3 <10 weeks, or premature <34 weeks due to eclampsia)
Plus persistently +ve antibody titres
Clinical features of anti-phospholipid and Mx?
Thrombus / pregnancy event
Livedo reticularis
Cardiac valve lesions
Thrombocytopaenia
Mx = heparin initially then warfarin
Warm AIHA - mechanism, causes, Ix and Mx?
IgG mediated at 37 degrees
Causes = SLE, RA, Evans and idiopathic
Ix = extravascular haemolysis, spherocytes and DAT+ve
Mx = steroids, immunosuppression and splenectomy
Cold AIHA - mechanism, causes, Ix and Mx?
IgM at 4-degrees
Causes = idiopathic, neoplasm and mycoplasma
Intravascular haemolysis, acrocyanosis and raynauds, DAT+ve for complement only
Mx = avoid cold and rituximab
What diseases and Ab’s associated with paroxysmal cold haemoglobinuria?
Measles, chickenpox and mumps
IgG Donath-Landsteiner Ab’s bind RBC’s in the cold, then haemolyse when rewarmed
PNH - mechanism?
Due to an acquired deficiency in glycoprotein-phosphatidylinositol = cell membrane more sensitive to complement
Also have lack of CD59 on platelet cell membranes = predisposes to aggregation = clotting
PNH - clinical features, Ix and Mx?
Pancytopaenia Haemoglobinuria Thrombosis = budd chiari syndrome Haemolytic anaemia Rarely can progress to aplastic anaemia
Ix:
Blood = pancytopaenic
Flow cytometry = low CD59 and CD55
Mx = blood product replacement, anti-coagulation and monoclonal antibody eculizumab
HUS - mechanism and causes?
Due to endothelial damage leading to microvascular thrombosis
90% occurs in children due to E.Coli 0157:H7
Pregnancy
Tumours
Drugs = ciclosporin and COCP
HUS - Clinical features, Ix and Mx?
Triad = acute renal failure, MAHA and thrombocytopaenia
+ bloody diarrhoea and abdominal pain
Ix = FBC will show anaemia and thrombocytopaenia. U+E’s plus stool culture
Mx:
Supportive = fluids, blood products and dialysis
No role for antibiotics
Plasma exchange in severe ones with no diarrhoea
TTP - mechanism?
Genetic or acquired defect in von Willebrand cleaving enzyme ADAMTS13
= large von willebrand multimers = platelet aggregation
TTP - clinical features, Ix and Mx?
Pentad: Fever MAHA Acute renal failure Thrombocytopaenia CNS signs - confusion and seizures
Ix = same as HUS = anaemia, thrombocytopaenia and fragmented blood film. U+E’s
Mx = plasmapheresis
What is the commonest inherited haemolytic anaemia in Northern Europe?
Inheritance pattern?
Hereditary spherocytosis
Autosomal dominant
Hereditary spherocytosis - Clinical features, diagnosis and Mx?
FTT, jaundice and pigment stones = colic
Splenomegaly
Aplastic crisis precipitated by parvovirus B12
Dx = osmotic fragility test.
- also spherocytes on the film and DAT-ve
Mx:
No splenectomy until age 6
Pre splenectomy vaccine course
After = BenPen and annual influenza + 5-yearly pneumococcal
Hereditary spherocytosis - mechanism ?
Defect in structural membrane proteins = abnormal cells = removed by spleen
G6PD deficiency - inheritance, mechanism and triggers?
Male X-linked disorder
Defect in pentose phosphate shunt = reduced NADPH production = RBC oxidative damage
Triggers for haemolysis:
Broad beans / lava beans, moth balls
Infection
Drugs = anti-malarial, ciprofloxacin and sulphonamides
G6PD deficiency - clinical features, investigations and management?
Neonatal jaundice, intravascular haemolysis, gallstones
Ix = film = irregularly contracted cells, bite cells, Heinz bodies
Mx = Treat cause / avoid precipitant
Transfusion
Pyruvate kinase deficiency - inheritance and mechanism?
Autosomal recessive
Defect in ATP synthesis = rigid red cells = removed in spleen
Pyruvate kinase deficiency = clinical features, Ix and Mx?
Jaundice, anaemia and splenomegaly (JAS)
Ix = PK assay, blood film > Burr cells and echinocytes
Mx often not needed. Can transfuse and splenectomy
Mechanism behind polycythaemia vera?
95% mutation in Jak2
Clonal proliferation of marrow stem cell = increased RBC. volume
Clinical features of polycythaemia vera ?
Hyperviscocity = headaches, visual disturbance and thrombosis
Pruritus after hot baths = histamine release
Splenomegaly and hepatomegaly
Haemorrhage
HTN
Mx of polycythaemia vera?
Aspirin, venesection
If high thrombosis risk = hydroxycarbamide = cytoreductive
Causes of secondary polycythaemia?
Hypoxia = COPD, altitude, smoking
EPO = renal cysts
Mechanism of essential thrombocytopaenia?
Sustained dysregulated production of megakaryocytic from bone marrow = increasing circulating numbers of platelets
Clinical features of essential thrombocytopaenia?
50% asymptomatic Thrombosis Bleeding Splenomegaly Burning pain in extremities on heat = erythromelalgia Livedo reticularis
Management of essential thrombocytopaenia?
Conservative = stop smoking, diet, exercise
Plateletpheresis
Medical - anti platelet e.g. aspirin
Mechanism behind primary myelofibrosis?
increased clonal proliferation of haematopoietic cells in bone marrow, particularly megakaryocytic.
These abnormal cells produce excess growth factor = excess fibroblasts = collagen deposition and fibrosis
This means fibrosis in bone marrow, cannot make cells there so become pancytopaenic
Also means extra medullary haematopoiesis = hepatomegaly and splenomegaly
Clinical features and investigations of primary myelofibrosis?
Old person, massive splenomegaly
Pancytopaenic = anaemia, infections and bleeding
Blood film = tear drop poikilocytes
Unobtainable BM aspirate, dry tap. Means need trephine biopsy
High rate and LDH
Prognosis of primary myelofibrosis?
Median 5-year survival
Management of primary myelofibrosis?
Asymptomatic = folic acid and pyridoxine, peginterferon alpha
Symptomatic = BM transplant, not if >65
Mechanism of sickle cell?
Abnormal synthesis of HbS
Glutamate substituted for non-polar valine = fragile and haemolyse
Clinical features of sickle cell anaemia?
SICKLED
Splenomegaly
Infarct = stroke, spleen, retinal floaters
Crises = pain
Kidney failure
Liver and. lung disease = SOB, jaundice, cough
Erection issues
Dactylitis
Crisis type in sickle cell?
Thrombotic = pain, could be any organ really
Sequestered = pooling of blood due to sickling in organs e.g. spleen or lungs
Aplastic crisis - due to parvovirus
Haemolytic crisis (rare)
Management of sickle cell?
Crisis = analgesia, hydrate, warm and oxygen
Antibiotics if infection
Exchange transfusion
Long term = Penicillin and immunisations, folate, hydroxycarbamide if multiple crises
Surgical complications of sickle cell?
Acute cholecystitis
Avascular necrosis
Bowel ischaemia
Mechanism of ALL?
Arrest of maturation of lymphoblasts and excessive production of immature lymphoblasts = no space for the other cells to form
Clinical features of ALL?
Common age of onset?
3-5 years
Pancytopenia = infection, bruising and anaemic
Bone pain
Splenomegaly and hepatomegaly due to extra medullary haematopoiesis
Testicular swelling
Investigations of ALL?
BM aspirate > 20% blasts
WCC raised, RBC/platelet/PMN low
XR / CT may show mediastinal LN’s
Management of ALL?
Supportive = fluids and allopurinol
- prophylactic antibiotic and permanent line for chemo
Induction chemo, consolidation and maintenance
Longer chemo in boys due to testes
Mechanism of AML?
Arrest of differentiation of the myeloblast at a point in it differentiation.
Can occur at any of multiple stages
Causes abnormal blast cells in peripheral blood and BM
Clinical features of AML?
Who it tends to affect?
Pancytopenia
Infiltration = hepatosplenomegaly, gum hypertrophy and bone pain
Increased WCC = hyperviscocity
adults
Ix and management of AML?
WCC high, RBC + platelets low
Film = peripheral blasts
BM aspirate > 20% blasts, Auer rods under MPO stain
Mx = supportive + chemo ± BMT/SCT
Commonest leukaemia in western world?
CLL
who does CLL affect?
Elderly males
Mechanism of CLL?
Monoclonal proliferation of mature lymphocytes - usually B-cells
Clinical features of CLL?
Often asymptomatic
Constitutional
Bleeding + infections
Infiltrates = splenomegaly + LN’s ++
Ix of CLL?
What would make it small lymphocytic leukaemia?
B lymphocytes > 5 x10^9
Clear cells
DAT+ve
SLL = B cells mainly in spleen, <5x10^9
What is Binet staging for, and the staging please maestro?
CLL
A <3 lymphoid areas = 12 year prognosis
B > 3 lymphoid ares = 5-year survival
C Hb or platelets <100 = 2 year survival
Management of CLL?
Supportive if Binet A+B
Chemo if Binet C
Mechanism of CML?
Myeloid hyperplasia
Due to philadelphia chromosome = t(9:22) translocation = BCR-ABL gene
Age of presentation for CML?
Clinical features?
60
Anaemia, bruising and bleeding
MASSIVE splenomegaly and hepatomegaly
Constitutive symptoms
Phases of CML?
chronic =. 80% progress to accelerated phase
Over production of mature neutrophils, basophils and myelocytes
Accelerated = 10-19% blasts
Blast phase = > 20% blasts. Basically AML
Ix and Mx of CML?
Raised WBC’s
Low Hb and platelets if in blast/accelerated phase
Raised urate levels
Phil+ve
Imatinib
Mechanism of NHL?
Lymphoma begins in lymphocytes = growth and expansion of monoclonal population of malignant lymphocytes
Risk factors for lymphoma?
Constant antigen stimulation:
- H. Pylori = MALT
- Coeliacs = Small bowel T-cell lymphoma
- Hashimotos
- Sjogrens
Infection:
HTLV1 infects T cells
EBV infects B cells
Hep C
HIV
Iatrogenic = immunosuppression following solid organ transplantation
NHL clinical features?
NHL Ix?
75% present with painless LN’s. Multiple sites and symmetrical
Splenomegaly
B-symptoms
Pancytopaenia
Hyperviscocity
LN and BM biopsy for classification
Staging with MRI/CT
Classification of NHL?
B-cell:
Aggressive:
diffuse large B cell
Burkitts
Indolent:
MALT
Follicular
T-Cell associated:
Adult T cell lymphoma
Enteropathy associated
Mx of NHL?
R-CAVP
Rituximab, cyclophosphamide, adriamycin, vincristine, prednisolone
Classic Burkitt’s NHL signs?
C-myc gene
Starry sky
Hodgkins lymphoma - bimodal distribution? Mechanism?
20-29 and >60
Lymphoma arising from mature B-Cells, but has reed Sternberg cells
Under the microscope what cells distinguish NHL vs HL?
Which has. better prognosis?
HL has reed-sternberg cells
HL has better prognosis
Types of HL and best vs worst prognosis?>
Nodular sclerosing = most common, 70%
Mixed cellularity = 20%, best prognosis
Lymphocyte predominant = 5%, BEST PROGNOSIS
Lymphocyte depleted = rare, worst prognosis
Clinical features of HL and staging?
LN's, painlessly, mainly cervical - in questions more pain on alcohol B-symptoms Pel-ebstein fever Hepato/splenomegaly
Ann-Arbour staging 1 = single LN region 2 = > 2 regions, same side of diaphragm 3 = >2 either side of diaphragm 4 = Spread beyond nodes
Ix for HL?
Mx?
LN excision > must be COMPLETE LN = reed sternberg cells
CT-CAP for staging
Chemo ABVD:
Adriamycin, bleomycin, vinblastine, DTIC
4-weekly cycles x6, preserves fertility
SE’s = pulmonary fibrosis and cardiomyopathy
Multiple myeloma mechanism?
Clonal proliferation of plasma cells = monoclonal IgG or IgA raised
Clones may produce free light chains
These can. be excreted via kidneys = Bence-Jones proteins in urine
Clone produce IL-6, inhibits osteoblasts and activates osteoclasts
Clinical features of multiple myeloma?
CRAB
Calcium raised
Renal impairment - acute tubular necrosis due to free light chains causing inflammation
Anaemia
Bone lesions = #’s and can get spinal cord compression
Ix for multiple myeloma?
Electrophoresis = monoclonal Ig
Urine = raised specific gravity
BM aspirate
X-ray = punched out lytic lesions
characteristics of Waldenstroms?
IgM only
Older men
Systemic upset, hyperviscocity + hepatosplenomegaly + LN’s
Mechanism of amyloidosis?
Extracellular deposition of an insoluble fibrillary protein = amyloid
Leads to organ dysfunction
Cause of AL amyloid vs AA?
AL = derived from plasma cells producing amyloidogenic light chain Primary = Occult plasma cell proliferation Secondary = Myeloma, MGUS, Waldenstroms
AA = from serum amyloid in chronic inflammation
RA, IBD, chronic infection
Clinical features of AA vs AL amyloidosis?
AL: Renal - nephrotic syndrome Heart - restrictive cardiomyopathy Nerve - Carpal tunnel, neuropathy GIT - Malabsorption, perforation Vascular - Periorbital purpura
AA:
Renal
Hepatosplenomegaly
Ix and Mx of amyloidosis?
Congo red stain = apple green birefringence
Serum amyloid precursor scan
SURGIAL BIOPSY OF RECTUM
Mx:
AL = treat myeloma
AA = Treat underlying cause
4 acute porphyrias?
Enzyme deficient in each?
Plumboporphyria, acute intermittent porphyria, hereditary coproporphyria, variegate porphyria
Plumboporphyria = ALA dehydratase /. PGB synthase
AIP = HMB synthase
Hereditary = coproporphyrinogen oxidase
Variegate porphyria = protoporphyrinogen oxidase
features of plumboporphyria?
PGB synthase
90% abdominal pain
Motor neuropathy
ONLY ONE WITH LOW PBG
Features of AIP?
HMB synthase
High ALA and. PBG
Abdominal pain, red urine on standing, motor neuropathy, HTN and tachycardia
Ix and Mx of AIP?
Deep red urine on standing with raised urinary porphobilinogen (PBG)
Raised serum levels of ALA and PBG
Mx = analgesia, fluids and IV haematin
Features of hereditary coproporphyria?
Coproporphyrinogen oxidase
coproporphyrinogen in stool
Neurovisceral symptoms as build up of coproporphyrinogen = HMB synthase inhibitors = ALA build up
Photosensitive skin, blistering and pigment change
Features of variegate porphyria?
Protoporphyrinogen oxidase
Build up of protoporphyrinogen in stool
Neurovisceral as it inhibits HMBS = ALA build up
Photosensitive skin, blistering and pigment changes
Non acute porphyria?
Porphyria cutanea tarda = uro. decarboxylase
Porphyria cutanea tarda - features, investigations and. Mx?
photosensitive rash, blistering, skin fragility
Hyperpigmentation
Classically occurs delayed post sun exposure
Urine = elevated uroporphyrinogen and pink colour under woods lamp
Mx = avoid sun, iron chelators + chloroquinine
Features of lead poisoning, what blood level is signifiant for diagnosis + management?
Abdo pain, peripheral neuropathy, constipation, blue lines on gum margin in 20%
> 10mcg/dl is signifiant
Mx = DMSA, penicillamine, EDTA
Indications for a splenectomy?
Trauma - hilar injury ITP AIHA Rupture e.g. EBV Hereditary spherocytosis Splenic vein thrombosis (diagnosed with CT angio)
Complications of splenectomy ?
Haemorrhage Pancreatic fistula Gastric ileus lower lobe left atelectasis Susceptibility to encapsulated organisms - strep pneumo, HI, meningococci
Outline of procedure for emergency splenectomy e.g. trauma?
Midline incision under GA
Pack all four quadrants
Remove packing and assess damage
If hilar injury or severe parenchymal injury = remove
divide the short gastric vessels and ligate
Clamp splenic artery and vein - double clamp on patient side as safety precaution
When done wash out abdomen, place drain
Some surgeons implant portion of spleen into the omentum
In splenectomy where do the short gastric arteries lie?
Why might you find amylase in your drain post-splenectomy?
When should you administer platelet transfusion in ITP splenectomy?
Within the gastrosplenic ligament
Damage to pancreatic tail
After clamping of splenic artery
Immunisations for splenectomy?
pneumovax, HiB, Men C and flu two weeks before surgery
Then yearly flu and 5-year pneumococcal
Penicillin V
Blood film signs of splenectomy?
Target cells
Howell Jolly bodies
Pappenheimer
Acanthocytes
Oncovirsues - EBV, HPV 16/18, HPV8, Hep, HTLV-1?
EBV = Burkitts, Hodgkins lymphoma, post-transplant lymphoma + nasopharyngeal carcinoma
HPV 16/18 = cervical anal penile and vulval cancer
HPV8 = Kaposi’s
HTLV-1 = Adult T-ell leukaemia
Hep B/C = hepatocellular carcinoma
Via vagus to the heart what do the parasympathetic fibres release?
What do the sympathetic fibres release?
Parasymp. = ACh
Symp. = noradrenaline. Noradrenaline binds to B1 receptors on SA node and increased depolarisation rate
4 phases of a myocardial action potential?
Phase 0 = rapid depolarisation > sodium influx
Phase 1 = early depolarisation > Potassium efflux
Phase 2 = plateau > Slow calcium influx
Phase 3 = final depolarisation > Potassium efflux
Phase 4 = restoration > Na/K/ATPase pump causes slow influx of potassium until threshold potential reached
Cardiac cycle - mid and late diastole, early and late systole?
Mid diastole = basically passive ventricular filling
AV valves are open, outflow valves shut. Ventricles hold 80% of final volume.
Aortic pressure is high.
Late diastole = active ventricular filling
Atria contract, ventricles get last 20% volume
Early systole = ventricular contraction
AV valves shut, ventricular pressure rises, contraction
AV valve bulges back into the atria = C-wave on JVP
Blood is ejected as pressures exceed aortic and pulmonary pressures
Atrial pressure will decrease as ventricles shorten and contract pulling them down = x-descent on JVP waveform
Late systole = ventricles relax
Pressure drops, brief period of retrograde flow then aortic valve closes
Atrial pressure begin to exceed ventricular > AV valve opens > passive filling begins
Atrial pressure falls here = Y-descent on JVP
Laplaces law?
For hollow organs, with circular cross section, total circumferential wall tension = pressure x radius /2
Total luminal pressure = radius x transmural pressure
Starlings law?
Increased in end diastole volume = larger stroke volume
Up to a point but stretch the cardiac tissue too much and then starts to decrease again
Where are baroreceptors located, what are their nerves they travel in and what stimulates them?
Aortic arch and carotid sinus
Aortic arch = via vagus
carotid sinus = glossopharyngeal
Stimulated by aortic stretch
What happens when baroreceptors are stimulated by aortic stretch?
Increased parasympathetic to SA node
Decreased sympathetic too…
Ventricular muscle = decreased contractility
Venous system = increased compliance
Decreased peripheral arterial vascular resistance
Where are atrial stretch receptors located?
In atria between junction of pulmonary veins and vena cava
Low pressure sensors
What happens when the atrial stretch receptors are stimulated?
Increased stretch = increased parasympathetic activity + release of ANP
If rapid filling causes increased HR = Bainbridge reflex
Decreased stretch = increased sympathetic activity = decreased renal blood flow, activates RAS system = sodium and water retention
JVP waveform - What is absent in AF?
What does this wave usually signify?
When might this wave be large?
a waves
Atrial contraction
Any cause of RVH e.g. pulmonary stenosis/HTN, tricuspid stenosis
JVP waveform - What do canon a-waves mean?
Extra large a waves, caused by atrial contraction against closed AV valve (tricuspid)
Compete heart block
JVP waveform - What does c-wave correlate with?
Tricuspid valve closure, where it bulges back into the atria on ventricular contraction
JVP waveform - what does x-wave mean?
x-descent
When ventricles contract they pull the atria down = decreased atrial pressure
JVP waveform - what does v-wave correspond to?
When might you see prominent V waves?
Passive atrial filling, increasing the atrial pressure against a closed tricuspid
Tricuspid regurgitation
JVP waveform - what is y-wave?
Why might you see a steep or shallow y-wave?
Y descent
opening of tricuspid and passive filling of ventricles
Shallow = tricuspid stenosis or RA myxoma Steep = RVF, constrictive pericarditis, tricuspid regurgitation
ECG - what does p-wave represent?
Atrial depolarisation
ECG - PR interval represent and time?
Time between atrial depolarisation and ventricular depolarisation
0.12-0.2 secs
ECG - what does the QRS complex represent?
Ventricular depolarisation
0.06 - 0.1 secs
ECG - what does T-wave represent ?
Ventricular repolarisation
Mechanism behind inotropes?
Aim to increase cardiac output
Catecholamine like agents, work by increasing cAMP levels via adenylate cyclase stimulation, which causes intracellular calcium mobilisation
This causes contraction
4 inotrope examples and the receptors they act upon?
Adrenaline = lower dose beta-adrenergic, higher dose alpha receptor Dopamine = renal and mesenteric vasodilation via D1/D2 Dobutamine = B1 Noradrenaline = A1
How the inotropic receptors act?
Alpha = vasoconstriction
B1 = increased cardiac output and HR B2 = Vasodilation D1 = Renal and mesenteric vasodilation D2 = inhibits noradrenaline release
what and where are the three respiratory centres?
Medulla, apneustic in lower pons + pneumotaxic in upper pons
What does each respiratory centre do?
Medulla: Inspiratory and expiratory neurones Ventral = forced voluntary expiration Dorsal = forced voluntary inspiration Depressed by opiates
Apneustic in lower pons
= stimulates inspiration - activates and prolongs
Pneumotaxic in upper pons
= Inhibits inspiration at a certain point
Where are your respiratory chemoreceptors found?
Peripherally = bifurcation of the aorta and carotid body
- Respond to low PO2, H+ increased, increased CO2 in arterial blood
Central = medulla
- responds to increased H+ in the interstitial fluid of brain
NOT INFLUENCED BY OXYGEN
Structure of haem?
What an iron bind to?
Protoporphyrin ring surrounding an iron atom
Iron an form two additional bonds - one with oxygen one with polypeptide chain
The polypeptide chain has 2 alpha and 2 beta subunits
Beta chains bind 2,3-DPG
Haldane vs BOHR effet
Haldane = oxygen curve to the left
- means at lower oxygen levels, Hb is more saturated = delivers less oxygen
BOHR = oxygen curve to the right = for a given oxygen level there is reduced saturation of Hb. = better oxygen delivery
What shifts the oxygen curve to the right?
CADET look RIGHT
CO2 increased Acidosis DPG increased Exercise Temperature increased
Borders of trachea?
Arterial supply?
C6 - T5
Inferior thyroid arteries
Tracheostomy - what does it increase and decrease?
Increase = alveolar ventilation
Decrease = Work of breathing, anatomical dead space, proportion of ciliated epithelial cells
What is functional residual capacity?
Equation?
Factors that increase it and decrease it ?
Volume of lung after normal expiration
FRC = RV + ERV
Decrease = upright, asthma, emphysema Increase = Obesity, pulmonary fibrosis, abdominal swelling, laparoscopic surgery, muscle relaxants
When do we see high lung compliance vs low?
High in old people and COPD
Low = pulmonary fibrosis, lack of surfactant, atelectasis
Alveolar ventilation - what is minute ventilation vs dead space ventilation?
Minute = total volume of gas ventilated per minute
Dead space = volume of gas not involved in exchange
Anatomical vs physiological dead space?
Anatomical = air not involved that sits in mouth, pharynx, trachea and bronchioles
Measured by fowlers method = inhale 100% oxygen, then measure nitrogen coming out
Increased in tall people, big people, bronchodilator people
Physiological is the gas not exchanged at alveoli
Increased in COPD, PE, hypotension
What is transfer factor?
Rate at which gas diffuses into alveoli
Result an be given as total gas transfer = TLCO
What affects TLCO?
Raised: Asthma Pulmonary haemorrhage L to R cardia shunts Polycythaemia Male and exercise
Decreased = pulmonary fibrosis/oedema/emboli Pneumonia Anaemia Emphysema Low cardiac output
Obstructive vs restrictive lung spirometry?
Obstructive = reduced FEV1, with normal / low FV FEV1:FVC = <70% LOW
Restrictive FEV1 normal, FVC low
FEV1:FVC >70%
Obstructive vs restrictive lung conditions?
Obstructive = Asthma, COPD, bronchiectasis
Restrictive = Pulmonary fibrosis, asbestosis, sarcoidosis, ARDS, kyphoscoliosis and neuromuscular disorders
Primary peristalsis vs secondary?
Primary is movement from oesophagus to stomach
Secondary = Food doesn’t enter the stomach stimulates stretch receptors = peristalsis
Of GI tract which has highest secretion go bicarb?
Pancreas at 115
Of GI tract what secretes the most chloride?
Stomach, then jejunum/ileum, then from the bile
Which part of GI that secretes the most potassium?
Duodenum
Salivary gland through to colon volume of secretions per day?
SG = 1.5L Stomach = 1.5L Duodenum = up to 2L Pancreas 1L Bile 500ml - 1L Jejunum / ileum 3L Colon 100ml
In vomiting why do you get hypokalaemia?
Due to renal wasting
Volume of K secretion is very low ins stomach, so hypokalaemia is not due to the vomiting itself
Ileostomy effluent?
22mmol/L K, 126 sodium
Gastric secretions - what do chief cells, surface mucosal cells and parietal cells secrete?
Chief cells = Pepsinogen
Mucosal cells = Mucous and bicarb
Parietal cells = Mg, Ca, Na, HCL + intrinsic factor
Phases of gastric acid secretion?
- Cephalic phase = smell and taste
30% acid produced
Vagal cholinergic stimulation = HCL + gastrin from G cells - Gastric phase = stomach distension
60% of acid
Stomach distension / low pH / peptides = GASTRIN RELEASE - Intestinal phase = food in duodenum
10% of acid produced
High acidity / distension / hypertonic solution in duodenum inhibits gastrin release via enterogastrones = CCK + secretin
What increases / decreases gastric acid secretion?
Increase = vagal stimulation, gastrin and histamine release
Decrease = CKK, secretin and somatostatin
Gastrin. - source, stimulus, inhibition and action?
G cells of antrum
Stimulus = distension and extrinsic
Inhibition = low pH and somatostatin
Action:
- Increase HCL, pepsinogen and IF secretion
- Cause histamine release from enterochromaffin cells
- Increase gut motility
- Trophic effect on gastric mucosa
Cholecystokinin (CKK) - source, stimulus and action?
I cells from upper intestine
Stimulus = partially digested proteins and triglycerides
Action:
- Increase enzyme rich pancreatic secretions
- Contraction of gall bladder and relaxation of sphincter of Oddi
- Decreases gastric emptying
- Trophic effect on acinar pancreatic cells
- Induces satiety
Secretin - source, stimulus and action?
S cells in upper small intestine
Acidic chime and fatty acids
Actions:
- Increased bicarbonate rich secretion from pancreas and hepatic duct cells
- Decreased gastric acid secretion.
- Trophic effect on pancreatic acinar cells
VIP - source, stimulus, action?
Cells in upper intestine / pancreas
Neural stimulation
Action:
- Decreases gastric acid secretion + pepsinogen
- Stimulates pancreatic and intestine secretions
Somatostatin - source, stimulus and action?
D cells from pancreas and stomach enterochromaffin cells
Stimulus = bile salts, fats and glucose in intestinal lumen
Action:
- Decreases insulin and glucagon
- decreases gastrin, pepsinogen and acid secretion
- Stops pancreatic secretions
- inhibits trophic effect of gastrin
- stimulates mucous production
Leptin vs grehlin?
Leptin produced by adipose tissue, induces satiety.
Stimulates MSH and CRH
Grehlin induces hunger, produced by fundus of stomach
Factors that increase gastric emptying?
Neuronal = mediated via vagus
Hormonal = gastrin
Factors that decrease gastric emptying?
Hormonal = Gastric inhibitory peptide, CKK, enteroglucagon
Iatrogenic = vagotomy or distal gastrectomy
In distal gastrectomy a posteiror retrocolic anastomoses empties better vs anterior
Diabetic gastroparesis = vagus neuropathy
- means metoclopramide won’t work as this affects vagus
Malignancy = stomach or pancreas
Pyloric stenosis
How would a somatostatinoma present ?
steatorrhoea
Diabetes mellitus
Gallstones
SE’s post gastrectomy?
Fast passage of food = abdo pain, diarrhoea and hypoglycaemia
Iron and B12 malabsorption
Osteoporosis
Mx = High protein, low carb diet
Replace B12, iron and calcium
Iron - where is it absorbed, how much gets absorbed, factors affecting absorption, how is it transported and stored, how is it excreted?
Absorbed in duodenum and upper jejunum
10% gets absorbed
Increased absorption = vitamin C and gastrin
Decreased = PPI’s, tetracycline and tannin
Transported as Fe3+ bound to transferrin
Stored in ferritin in the BM
Excreted via intestinal tract
Ileum vs jejunum?
Ileum = one lucky cookie and has double layer of arcades
Also has more mesenteric fat
Thinner walled
Role of ileum ?
what would happen in resection and Mx?
Absorption of vitamin B12 and bile salts
Neuroendocrine cells release hormones
Risk of bile salt malabsorption
Diarrhoea and stones
Lack of B12 predisposes to macrocytic anaemia
Mx = cholestyramine
Pancreatic exocrine cells: Acinar vs ductal?
Acinar = enzymatic Trypsinogen Amylase Procarboxylase Elastase
Ductal = aqueous secretion
Sodium, bicarb, water K and chloride
Regulation of pancreatic exocrine secretion?
Digested material = CKK and Ach = stimulates ductal and acinar = enzymes etc
CKK most potent
Ductal cells also stimulated by secretion from S cells in upper duodenum
Bile - how much produced per day, what makes up bile?
500ml - 1500ml
Bile salts, bicarb, steroids, cholesterol and water
Bile salts - Reabsorption, primary vs secondary?
90% reabsorbed in terminal ileum to the liver
Primary = chelate and chenodeoxycholate
Secondary = Bacterial action on the primary ones = deoxycholate and lithocholate
Deoxycholate reabsorbed
Lithocholate excreted
Which is the active thyroid hormone?
T3
How are T3/T4 formed?
Thyroid actively concentrates iodine, this is then oxidised by peroxidase in follicular cells > atoms iodine
This then iodinates tyrosine residue in thyroglobulin
Iodinated tyrosine undergoes coupling > T3/T4
Which cells secrete PTH?
Chief cells of the parathyroid gland
Effect of PTH?
- active reabsorption of calcium. and magnesium from DCT
- Increases activation of vitamin D = increased intestinal reabsorption of calcium
- Binds osteoclast = resorption of bone
Pancreatic endocrine function?
B cells = insulin
Alpha = glucagon
Delta = somatostatin
F cells = pancreatic polypeptide
Insulin - estruture, half life, function and production?
Peptide hormone from B cells
Half life = 30 minutes
Causes glucose absorption by skeletal muscle, liver and fat tissue
Pro-insulin is formed in rough ER of B cells
Cleaved to form insulin and peptide C
What common drug can inhibit insulin release?
BB’s
Glucagon - action, stimulation and inhibition?
increase plasma glucose levels
Stimulation: Decreased glucose levels Increased catecholamine or amino acids Sympathetic nervous system ACh and CKK
Inhibits it:
Somatostatin
Insulin
Free fatty acids and keto acids
Stress response to surgery - overall changes?
Muscle protein loss
Sodium and water retention
Suppression of anabolic steroid production
Activation of sympathetic nervous system
Stress response to surgery - Sympathetic system, vascular endothelium and normal changes?
Noradrenaline from symp, adrenaline from adrenal medulla = catecholamines = HTN and tachy
Also causes bronchoconstriction, reduced gut motility. and increased glucagon
Vascular endothelium releases NO = dilation
PGE’s also induce dilation and platelet aggregation
Hormonal changes:
Decreased - insulin, testosterone and oestrogen
No change - TSH, LH + FSH
Increased - GH, prolactin, ACTH, ADH, cortisol, aldosterone and renin, glucagon
Stress response to surgery - specific hormonal response with cortisol, ADH, insulin and GH?
Cortisol = increased significantly within 4-6 hours
No negative feedback = raised ACTH and cortisol
Effects:
1. Increased muscle breakdown and lipolysis
2.MR effect
3. reduced inflammatory effect
4. anti-insulin
ADH = more renin = more angiotensin = more aldosterone = sodium and water retention
Insulin - B cells inhibited by the alpha 2 adrenergic effects of catecholamines
GH = increased post surgery
Stops muscle breakdown and promotes tissue repair via insulin growth factors
Stress response in surgery - carbohydrate, protein, lipids, salt and water + cytokines?
Carbs = high as no insulin and catecholamines and cortisol = gluconeogenesis and glycogenolysis
NOT GOOD AS IMPAIRS WOUND HEALING + INFECTIONS
Proteins = initially only anabolism inhibited, later severe catabolism. Amino aids used for auto phase proteins
Lipids = lipolysis and ketone production
Due to increase in catecholamines and. cortisol, with lowered insulin
Salt and water - retained due to increased ADH and renin
cytokines - IL-6 is the main one, also IL-17
Peak 12-24 hours
Stress response to surgery. - how an we modify it?
Opioids - cause suppression of hypothalamus and pituitary
However at too high a dose they can prolong recovery
Good nutrition
Spinal anaesthesia = reduce glucose, ACTH, GH and cortisol
Anabolic steroids and GH can help
Normothermia - lowers metabolic rate
Outline the RAAS?
Renin produced in kidney (juxtagolmerular apparatus) In response to hypotension, low sodium, catecholamines and erect posture
Renin converts angiotensinogen in liver to AT1.
ACE from lung converts AT1 > AT2
AT2 ultimately results in sodium and water retention via:
- acts on arterioles = vasoconstriction
- Acts on pituitary to release ADH = collecting duct water reabsorption
- Increases sympathetic activity
- Causes aldosterone secretion = tubular Na and water retention
Factors stimulating and inhibiting renin production?
Increasing: Low sodium Hypotension Erect posture Catecholamines
Decreasing = BB’s and NSAIDs
Glomerular function?
Filter
Basement membrane has poor allows smaller molecules to freely diffuse, larger -ve molecules e.g. albumin cannot
Typical GFR, equation?
125mls/min
(Conc. of solute in urine x volume of urine in. 1 min) / Plasma conc.
Where is calcium reabsorbed in the kidney?
DCT under the effect of PTH
The nephron - PCT main role and what is reabsorbed / excreted?
Main role if reabsorption of filtrate
Reabsorbs = 100% amino acids + glucose, 65% Na + H20, 90% of HCO3
BICARB reabsorbed via the HCO3
Excretes - urea and organic acids e.g. antibiotics
The nephron - role of loop of Henle?
Concentration of urine
Thin descending. limb = water reabsorption as highly water permeable. Creates gradient
Thick ascending limb = reabsorbs NACl
The nephron - DCT role and what is absorbed / excreted?
pH and calcium reabsorption
Calcium reabsorbed under affect of PTH here
Sodium and water also reabsorbed
The nephron - Collecting duct role and what acts here?
Water and K regulation
Na reabsorption coupled with K/H excretion
Aldosterone sensitive Na/K pump here
Also have aquaporin 2 channels controlled via ADH
How do carbonic anhydrase inhibitors work, an example, SE’s?
Block the reabsorption of carbon anhydrase in PCT, and thus. small amount of Na
Acetazolamide
SE’s = metabolic acidosis, stones, ataxia
How do loop diuretics work and SE’s?
e.g. furosemide
Block the Na/K/Cl transporter in thick ascending limb of loop of Henle
= excrete NaCl (also lose K and Ca)
SE’s = hypokalaemia, metabolic acidosis and ototoxic
How do thiazides work and SE’s?
What condition should you not use thiazides in?
Block the NaCl transporter in DCT = more excretion
Causes more calcium reabsorption
SE’s = hypokalaemia, hyperglycaemia and increased urate
Don’t use in gout
K sparing diuretics - 2 examples and SE’s?
Spiro = aldosterone antagonist
Aldosterone usually causes K excretion for Na reabsorption
Amiloride = blocks the luminal Na channel in DCT and CD
SE’s = hyperkalaemia and anti-androgenic = gynaecomastia
What cells produce catecholamines in the adrenal medulla, and what nerves innervate them?
Chromaffin cells secrete noradrenaline and adrenaline
Innervated by splanchnic nerve:
- preganglionic sympathetic fibres secrete Ach causing chromatin cells to exocytose contents
Structure of adrenal cortex?
What excretes the two products of the G and F
GFR
Glomerulosa = aldosterone
Fasciculata = glucocorticoids
Reticularis = androgens
Liver excretes glucocorticoids and aldosterone
What are corticosteroids made from and how do they exert their effect?
Corticosteroids affects?
Synthesised from cholesterol in the adrenal cortex
Act upon specific intracellular receptor in the nucleus = affects gene transcription
Metabolic = gluconeogenesis and decreased uptake of glucose, protein breakdown and lipolysis
Regulatory = -ve feedback to hypothalamus, decreased vasodilation, osteoclast activity increased and subdues inflammation
Adrenaline affects?
Alpha receptors = decreased insulin production, stimulate glycogenolysis and glycolysis
B receptors = stimulate glucagon, ACTH and lipolysis
Renal stones - calcium oxalate: radiography and RF’s?
Radio-opaque
Hypercalciuria is big RF
Renal stones - cystine - mechanism, classic features?
Inherited recessive disorder of transmembrane cystine transport = decreased absorption from intestine and kidneys
Multiple stones
Radio-dense as contain sulphur
Renal stones uric acid - Mechanism, RF’s, stones?
Product of purine metabolism
Low urinary pH, disease with extensive tissue loss e.g. malignancy
Radiolucent stones
Renal stones - calcium phosphate - causes and stones?
May occur in RTA, specifically type 1 and 3
High urinary pH
Radio-opaque
Renal stones - struvite - what makes them up, mechanism and stone?
Ammonium, magnesium and phosphate = staghorn
Due to urease producing bacteria = chronic infection = proteus mirabilis
Under alkaline conditions - crystals
Radio-opaque
Clinical features of low sodium ?
confusion, irritability and headache
Severe = Seizures + coma
Classification of low sodium?
Based on fluid status
Hypovolaemic hyponatraemia?
You lose Na and H20, but reabsorb mainly H20 with ADH
PC = postural drop, thirst + tachycardia
Urinary na >20 = renal = Thiazides or salt losing nephropathy
Urinary Na < 20 = extra renal = D+V, burns, fistula
Euvolaemic hyponatraemia?
SIADH e.g. lung cancer, meningitis, head trauma, drugs e.g. sulphonylureas and SSRI’s
Urine osmolality > 500
Adrenal insufficiency = Addisons = low cortisol = lBP = ADH release
Hypothyroid = reduced heart contractility = reduced CO = ADH release
Hypervolaemic hyponatraemia?
Raised JVP, bibasal creps + oedema
Heart failure = low BP = ADH
Liver cirrhosis = NO release = vasodilation = BP drops = ADH release
Kidney failure
Commonly seen in surgery due to overuse of IV dextrose
Hypernatraemia - causes, Ix and Mx
Usually due to dehydration
- Unreplaced water loss = GI losses, diabetes diuresis or DI
Ix:
Check blood sugars for diabetes
Check urine osmolality - if >700 excludes DI
Water deprivation test - if still can’t concentrate urine = DI
Give Desmopressin - if helps =. cranial, if doesn’t work = nephrogenic
Mx = IV dextrose
lab features of dehydration ?
Hypernatraemia Raised haematocrit Creatinine up Urinary sodium > 20 Metabolic acidosis Lactate high Urine osmolality increased
Hypokalaemia - clinical features and specific ECG changes?
Tetany and cramps
Muscle weakness, hyporeflexia
Arrhythmias
ECG - Flattened T-waves, prominent u-waves, long PR interval
Hypokalaemia 4 causes?
- Renal loss = RTA, thiazides / Gittlemans + Loop/Barters
- GI loss
- Excess aldosterone - Conns
- Redistribution - Salbutamol, insulin
Mx of hypokalaemia?
3-3.5 = oral KCL, recheck
<3 = IV KCL, max 10mmol/hour
Treat cause
Clinical features of hyperkalaemia and specific ECG changes?
Palpitates, chest pain and weakness
ECG = Tented T waves, flattened P waves, broad QRS
Causes of hyperkalaemia?
- Renal:
- Low eGFR = no filter > basically any cause of renal disease then
- RTA - Drugs = NSAIDS, ACEI, ARBS, spiro (also heparin and ciprofloxacin)
- low aldosterone = Addisons
- cellular redistribution = rhabdomyolysis e.g. burns, any acidosis
- Massive transfusion
Mx of hyperkalaemia?
10ml 10% calcium glucoate
50ml 50%dextrose + 10IU of insulin
Salbutamol nebs
How does PTH increase calcium?
- via activating 1,25-(OH)2.D
= Increases bowel reabsorption and renal reabsorption
= Osteoclastic activity at high levels
PTH does not directly bid to osteoclasts, but sends signal via osteoblasts
What might happen to PTH levels post parathyroid surgery?
Drop = hypocalcaemia
Neuromuscular irritability + laryngospasm
Give calcium gluconate ASAP
What cells produce calcite and how does it work?
Secreted by thyroid C cells
Inhibits:
Intestinal reabsorption
Osteoclast activity
Renal tubular reabsorption
Causes of low calcium?
PTH driven = low PTH:
Autoimmune hypoparathyroid
Di Georges = Cleft palate, abnormal facies, thymus aplasia, cardiac, hypocalcaemia, Chr 22
not PTH driven = high/normal
= Vitamin D low, chrnic renal failure, malabsorption
Features of low calcium?
Muscle spasm, seizure, chvosteks/trousseaus
How does albumin affect calcium?
Calcium bound to albumin > Low albumin = low calcium
Alkalosis = albumin protonation. = low calcium
Dystrophic calcification vs metastatic?
Dystrophic = calcium deposits in tissues that have undergone damage / degeneration
Normal serum calcium levels
e.g. breast cancer
Metastatic = normal tissue, high serum calcium
Hypomagnesaemia - Causes and features?
Causes: Diuretics TPN Low calcium and K Diarrhoea Alcohol
Features = Paraesthesia, tetany, seizures, arrhythmias, reduced PTH
How are calcium and mg linked?
Low magnesium can cause low PTH and means it cannot act on target cells
Hyperuricaemia - causes?
Either increased synthesis or decreased excretion
What causes increased synthesis of uric acid?
Lesch-Nyhan Myeloproliferative disease Exercise Psoriasis Cytotoxics
What causes decreased excretion of uric acid?
Drugs = CANT LEAP Ciclocporin Alcohol Nicotinic acid Thiazides Loop diuretics Ethambutol. Aspirin Pyrazinamide
Pre-eclampsia
Renal failure
Lead
Vitamin deficiency: A
Night blindness, epithelial atrophy and infections
Vitamin deficiency: B1
Thiamine
Beri Beri
Wet = tachycardia, SOB ad leg swelling
Dry = neuro signs - can’t move legs, numbness and tingling
Vitamin deficiency: B2
Dermatitis
Photosensitivity
Vitamin deficiency: B3
Pellegra
3D’s = dementia, dermatitis and diarrhoea
Vitamin deficiency: B12 - causes, features and Mx
causes = Pernicious anaemia, post-gastrectomy, poor diet, terminal ileal disease
Features = Macrocytic anaemia, sore tongue , neuro e.g. ataxia, neuropsychology e.g. mood
Mx = 1mg IM 6 times over two weeks, the 3 monthly
If folic acid too, replace the B12 first to avoid SCDC
Vitamin deficiency: C
Poor would healing, impaired collagen synthesis
Vitamin deficiency: D
Rickets / osteomalacia
Vitamin deficiency: K
Clotting disorders
If jaundiced = impaired absorption
What vitamin is needed for collagen synthesis, what cells produce collagen?
Vitamin C needed for hydroxylation of proline
Produced by fibroblasts
Collagen disease - Osteogenesis imperfects types? Symptoms?
Defect in collagen type 1
Fractures and loose joints
Subtypes:
Type 1 = normal collagen, insufficient amounts
Type 2 = Poor quantity and quality
Type 3 = Normal quantity, poor quality
Type 4 = sufficient quantity, poor quality
Collagen disease - ED - abnormality?
Abnormality in type 1 and 3
What is refeeding syndrome?
poor feeding = risk of low K/Mg/PO4 = organ failure
If not fed for >5 days, what % calories should we start at?
50%
High risk of refeeding?
BMI <16
Weight loss >15% over 3-6 months
Little PO > 10 days
Electrolyte abnormality
Mx of refeeding?
Thiamine and B12
Slowly increase PO intake
Monitor electrolytes
In hypovolaemic shock, what urinary sign do you see?
Increased urine specific gravity
Why does angiogenesis occur In wound healing?
Due to endothelial cell proliferation
Which cardiovascular receptor does dobutamine show a preference for?
B1 cardioreceptor = increased cardiac contractility and HR
How does T3 work?
Binds to nuclear receptor chromatin. = protein synthesis
Causes of increased anion gap acidosis?
MUDPILES M - Methanol U - Uraemia D - DKA P - Paraldehyde/phenformin I - Iron L - Lactic acidosis E - Ethylene glycol S - Salicylates
Best measure of renal plasma flow?
Para-amino hippuric acid (PAH)
Does adrenaline cause coronary vasospasm?
No
It doesn’t affect the B2 cardiac receptors which = vasospasm
Its cardiacs effects are mediated by B1
Causes of pseudohypernatraemia?
Multiple myeloma, hyperlipidaemia, high glucose
Major functions of the spleen?
- Filtration of abnormal blood cells and foreign bodies such as bacteria.
- Immunity: IgM. Production of properdin, and tuftsin which help target fungi and bacteria for phagocytosis.
- Haematopoiesis: up to 5th month gestation or in haematological disorders.
- Pooling: storage of 40% platelets.
- Iron reutilisation
- Storage monocytes
5 drugs that use pseudohaematuria?
Rifampicin, phenytoin, levodopa, methyldopa, and quinine
Which amino acids are catecholamines derived from?
Tyrosine
