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Chapters summarized in this work: Anemia Hemostasis Lung diseases Respiratory Failure Renal Diseases Renal Failure Jaundice Pancreas Problems Portal CirculaCon Arrhythmias Cardiomyopathies Valvulopathies

It is a very fast, quick review of the whole thing It is not a complete work for Your prepara;on, but a useful pre-exam lecture Based on Doc. Jipas material and Robbins Pathology Alessandro MoIa, UVVG, 3rd year

Blood Components: Plasma: 55%; Blood Cells: 45% Three types: Erythrocytes/RBCs Leukocytes/WBCs Thrombocytes/Platelets

Hematopoiesis is the process by which mature blood cells are generated and funcConal, assuming the existence of cells of origin who have a long series of transformaCons and hematopoeCc microenvironment (composed of stromal cells and sCmulaCng factors). Bone marrow is the central component generaCng blood cells: red cells, granulocytes, monocytes, lymphocytes, platelets and hematopoieCc funcCons are proliferaCon, dierenCaCon and cell release into circulaCon. Bone marrow consists of: reCculovascular stroma (with supporCng role, nutriCon and movement of hematopoieCc cells); medullar parenchyma - composed of acCve cells forming islands of hematopoiesis, usually arranged around a trophic cell - "nurse cell." Nurse cells are involved in erythropoiesis (iron stores) in myelopoesis and megacaryopoesis (liberate sCmulaCng factors - e.g.. IL-3). Pluripotent stem cells (PSCs) are the cells of origin of all blood cells.

The RBC life cycle: In the bone marrow, erythropoieCn enhances the growth of dierenCaCon of burst forming units-erythroid (BFU- E) and colony forming units-erythroid (CFU-E) into reCculocytes. ReCculocyte spends three days maturing in the marrow, and then one day maturing in the peripheral blood. A mature Red Blood Cell circulates in the peripheral blood for 100 to 120 days. Under steady state condiCons, the rate of RBC producCon equals the rate of RBC loss. What is anemia?Is a pathological state, accompanied by decrease in: the level of hemoglobin, the quanCty of erythrocytes, per unit of volume of the blood. Result: deciency in the oxygen-carrying capacity of the blood (hypoxia) Hemoglobin = grams of hemoglobin per 100 mL of whole blood (g/dL) Hematocrit = percent of a sample of whole blood occupied by intact red blood cells RBC = millions of red blood cells per microL of whole blood MCV = Mean corpuscular volume If > 100 MacrocyCc anaemia If 80 100 NormocyCc anaemia If < 80 MicrocyCc anaemia RDW = Red blood cell distribuCon width = (Standard deviaCon of red cell volume mean cell volume) 100 ; Normal value is 11-15%; If elevated, suggests large variability in sizes of RBCs Hgb:Women: <12.0 / Men: < 13.5 Hct: Women: < 36 /Men: <41 Symptoms and Clinical ManifestaDons: Decreased oxygenaDon: ExerConal dyspnea, Dyspnea at rest, FaCgue, Bounding pulses, Lethargy, confusion Decreased volume: FaCgue, Muscle cramps, Postural dizziness, Syncope Clinical ManifestaDons: 1. Pallor. 2. FaCgue, weakness. 3. Dyspnea. 4. PalpitaCons, tachycardia. 5. Headache, dizziness, and restlessness. 6. Slowing of thought. 7. Paresthesia. Physiologic Response to Anemia: Increased heart rate, Increased, stroke volume, VasodilaCon, Decreased oxygen anity (right shil in oxygen-hemoglobin dissociaCon curve) 2

Hypochromic combined mechanisms

Anemias ClassicaCon

Normochromic Hyperchromic

Decreased producDon of red blood cells AplasCc anaemia: ErythropoieCn deciency. Marrow inltraCon- malignancy: injury- infecCons, toxins; NutriConal deciency (iron, proteins); IneecCve erythropoesis(thalassemias); Labs: Low reCculocyte count, variable MCV.

Loss of red blood cells (bleeding, lysis) In blood Loss: ReCculocyte count usually elevated, bone marrow trying to compensate, MCV usually normal to slightly elevated. For Hemolysis: Acquired, Autoimmune process, vessel injury, Inherited RBC defect, ReCculocyte count usually elevated, MCV normal to slightly elevated

MicrocyDc Iron deciency, Thalassemia, Chronic disease, Copper deciency

NormocyDc Malignancy, Chronic disease, Renal failure, Blood loss, HemolyCc disorders, Hemoglobinopat hies

MacrocyDc Folate deciency, Vitamin B12 deciency, Inherited bone marrow failure, Hypothyroidism, Drug induced, AcCve hemolysis

ComplicaCons in Anemic Syndrome: biochemical changes, hemodynamic changes, respiratory and renal changes, alteraCons of Cssue perfusion, increased producCon of RBCs, immune system abnormaliCes and endocrine changes (hypofuncCons). AplasDc Type Is characterized by Pancytopenia (lowering of all blood cells types). Could be congenital or acquired, has a very low incidence and can be managed by EPO or blood transfusion. CriCcal in blood loss and sepsis. Iron deciency is the most common cause of anaemia, 20% of women (50% of pregnant women) and 3% of men do not have enough iron in the body. DisrupCon of iron metabolism causes anaemia and disturb cytochromes acCvity (cell respiraCon). Iron is obtained through dietary intake (muscle, liver) and iron absorpCon requires the presence of HCl and transferrin. Iron is absorbed in proximal small bowel. It may installs aler small and conCnuous loss of blood, inadequate intake, metabolism disorders or in situaCons of increased needs (pregnancy). Lab ndings: Serum Iron =LOW (< 60 micrograms/dL). Total Iron Binding Capacity (TIBC) = HIGH ( > 360 micrograms/dL). Serum FerriCn= LOW (< 20 nanograms/ mL). IT IS A MACROCYTIC HYPOCRHOMIC CONDITION !!! DestrucCon or hemolysis of RBCs at a rate that exceeds producCon, third major cause of anemia. Can be intrinsic if the problem stands to the hemoglobin itself or extrinsic if caused by external factors (normal RBC). Can be subdivided in: Hereditary spherocytosis, (G6PD) Deciency, ThromboCc Thrombocytopenic Purpura, HemolyCc Uremic Syndrome, Autoimmune HemolyCc anaemia, or can be triggered by infecCons (malaria, babesiosis, sepsis) and traumas (snake bites) Lab ndings: Increased indirect bilirubin, Increased LDH, Increased reDculocyte count, reduced/absent haptoglobin 3

Iron Deciency


Anemia in chronic diseases

UnderproducCon of RBCs, shortening of RBC survival , 2nd most common cause of anaemia (aler iron deciency anaemia. Generally develops aler 1-2 months of sustained disease. It is a normochromic, normocyCc or hypochromic, microcyCc anaemia, which develops through mulCple mechanisms. Newest name, inamma&on associated anaemia, is more representaCve because it reects pathophysiological mechanisms. Could be secondary (chronic infecCons, collagen diseases, malignancies, elderly paCents). Iron replacement is not necessary. May benet from erythropoieCn supplementaCon. Vitamin B12 and folic acid are important nutrients required in the process of nuclear maturaCon. They are required during erythropoiesis (during DNA synthesis). These anaemias may be caused because of a nutriConal deciency or impaired absorpCon mainly. Impaired DNA synthesis leads to defecCve cell maturaCon and cell division. Nuclear maturaCon delays from the cytoplasmic maturaCon NUCLEO-CYTOPLASMIC ASYNCHRONY. Abnormally large erythroid precursors and red cells. Cobalamin (Vit B12) deciency is formerly known as Pernicious Anemia. Anaemia is normochromic, macrocyCc dened by increasing MCV over 100 -> Macrocytosis is typical in: MegaloblasCc anaemia, Alcoholism, Liver disease. Megaloblas;c anaemia is characterized by nucleo-cytoplasmic asincronism due to deciency in DNA synthesis with normal RNA and protein synthesis (immature nuclei and mature cytoplasm).

Megalobl asDc subtype

Thalassemia EDology: Autosomal recessive geneCc disorder of inadequate producCon of normal hemoglobin weakening and destrucCon of red blood cells. PaCents have defects in either the or globin chain (unlike sickle-cell disease, which produces a specic mutant form of globin), causing producCon of abnormal red blood cells.Found in Mediterranean ethnic groups. Clinical ManifestaDons: AsymptomaCc -> major retardaCon -> life threatening: Splenomegaly, hepatomegaly.

Four Stages 2 3 4 1

The process by which the body stops bleeding upon injury and maintains blood in the uid state into the vascular compartment. Process is rapid and localized. It is ruled by: blood vessels, platelets and plasma proteins (coagulaCon, brynolyCc, serine protease inhibitors). And other minor processes like Kinin and Complement systems.

Primary hemostasis: Response to vascular injury (vasoconstricCon), FormaCon of the platelet plug adhering to the endothelial wall, Limits bleeding immediately

Secondary Haemostasis (coagulaCon): results in formaCon of a stable clot. Involves the enzymaCc acCvaCon of coagulaCon proteins that funcCon to produce brin as a reinforcement of the platelet plug (FIBRIN CASCADE). Gradually the stable plug will be dissolved by brinolysis. Clot RetracCon Fibrinolysis prevents excessive thrombus (clot) formaCon. It is acCvated by sCmuli that acCvate the Intrinsic pathway (exposure to subendothelial collagen and the platelet plug). Plasminogen is acCvated and becomes Plasmin, which is responsible for lysis of a clot; as well as inhibiCon of platelet aggregaCon and acCvaCon of cloyng factors in the aected area

Fibrinolysis to dissolve the clot Platelets

They interact with injured vessel wall, interact with each other to produce the primary hemostaCc plug, which is fragile and can easily be dislodged from the vessel wall. Are Small, anucleated cytoplasmic fragments, released from megakaryocytes in the bone marrow. Megakaryocyte proliferaCon is sCmulated by thrombopoieCn (TPO). Normal platelet count is 150-400 x 109/L. Survive 9-12 days. Nonviable or aged platelets removed by spleen & liver. 2/3 of platelets circulate in the peripheral blood; 1/3 are sequestered in the spleen. Spontaneous hemorrhaging occurs when platelet count gets < 10 x 109/L. Adhesion Process Shape Change AggregaDo n SecreDon Damage to endothelium exposes blood to the subepithelial Cssue matrix with adhesive molecules. Platelet receptor GPIb binds to subendothelium collagen bers through von Willebrands factor (vWF).Platelet adherence stops the iniCal bleeding Following vessel injury and platelet exposure to external sCmuli, platelets change shape from circulaCng discs to spheres with pseudopods. Shape change is mediated by an increase in cytosolic calcium. Exposure of platelet membrane phospholipids promotes the assembly of vitamin-K dependent factors on the platelet membrane surface. AcCvated platelets adhere to exposed collagen Platelet-to-platelet interacCon: begins 10-20 seconds aler vascular injury and platelet adhesion. Requires dense granule release from the adhering platelets. Requires Ca++ and ATP. Requires brinogen and brinogen receptors GPIIb and IIIa Secondary aggregaCon begins with platelet secreCon of dense granules, these contain large amounts of ADP that binds to the platelet membrane triggering the synthesis and release of TXA2. The release of large amounts of ADP combined with TXA2 amplies the iniCal aggregaCon of platelets into a large platelet mass 5

Bleeding Disorders
Platelets disorders producCon destruction (Primary/Idiopathic: ITP Acute/Chronic OR Secondary: Drugs, HIV) Clinical signs: Petechiae, ecchymoses, haematomas Bleeding from mucosal surfaces (epistaxis, gingival bleeding, hematuria, melena, hematochezia, hyphema) Prolonged bleeding aler venipuncture or minor surgery In theory, spontaneous bleeding as a result of primary haemostaCc defect could be due to one of three mechanisms: vascular defect, thrombocytopenia (most common) or thrombopathia CloZng factors abnormaliDes Congenital: Von Willebrand disease (MC with minimal bleeding), Factor VIII Deciency (Hemophilia A or Classic Type), Factor IX Deciency (Hemophilia B) Acquired: Vit. K deciency =Due to decient carboxylaCon of factors II, VII, IX &X; Oral anC-coagulant; Coumarin derivaCves= warfarin inhibit Vit. K factors. Liver diseases synthesis of factors. 1. Thrombosis of small, midsize vessels and organ failure 2. Contributes to mulCple organ failure in conjuncCon with haemodynamic and metabolic consequences Severe bleeding

Vascular abnormaliDes Causes: InfecCons (Meningococcemia, Rickesioses , InfecCve endocardiCs) Drug ReacCons Hereditary hemorrhagic telangiectasia Cushing syndrome Henoch - Schnlein Purpura Scurvy and the Ehlers-Danlos syndrome Amyloid inltraCon of blood vessels DIC= disseminated intravascular coagulaDon Is a state/syndrome which is characterized by accelerated intravascular coagulaCon associated with increased consumpCon of platelets and plasma cloyng factors. CharacterisDc features: acCvaCon of coagulaCon system acCvaCon of brinolyCc system consumpCon of cloyng factors consumpCon of natural inhibitors Thrombocytopenia Its course is determined by: platelet producCon vs destrucCon; brin deposit vs brinolysis; synthesis of coagulaCon factor versus their depleCon 6

In the DIC: Systemic acDvaDon of CoagulaDo n

Intravascular Deposit of brin DepleDon of platelets/ coagulaDon factor

and also

Vitamin K deciency

Factors II, VII, IX, X are all K-vitamin dependent. Synthesis of Vitamin K-dependent factors occurs in the liver. Vitamin K is an essenCal cofactor (for carboxylaCon) to acCvate these factors. AnCcoagulant rodenCcides interfere with recycling of Vitamin K, resulCng in rapid depleCon. Proteins C and S are also vitamin K-dependent. Clinical scenario: ObstrucCve jaundice, Fat mal-absorpCon, Broad spectrum anCbioCcs, Hemorrhagic disease of newborn. CoagulaDon tests: ProlongaCon of PT and APTT, normal TT Haemophilia A (factor VIII deciency) is the most common form of the disorder, present in about 1 in 5,00010,000 male births; amount or acCvity of factor VIII; factor VIII = cofactor for acCvaCon of factor X in the coagulaCon cascade. Haemophilia B (factor IX deciency) occurs in around 1 in about 20,00034,000 male births; Clinically= indisCnguishable from Hemophilia A with similar lab ndings; Diagnosis by factor IX levels. Like most recessive sex-linked, X chromosome disorders, haemophilia is more likely to occur in males than females. Haemophilia lowers blood plasma cloyng factor levels of the coagulaCon factors needed for a normal cloyng process. Thus when a blood vessel is injured, a temporary scab does form, but the missing coagulaCon factors prevent brin formaCon, which is necessary to maintain the blood clot. VWFactor is produced by megakaryocytes and endothelial cells, and it circulates in plasma complexed to factor VIII It is important in the formaCon of the primary platelet plug (causes platelets to adhere to subendothelial carClage). Von Willebrand factor's primary funcCon is binding to other proteins, in parCcular factor VIII, and it is important in platelet adhesion to wound sites; it is not an enzyme and, thus, has no catalyCc acCvity. Severe damage to hepatocytes or obstrucCon of bile duct results in variable factor deciencies and/or abnormaliCes in Vitamin K metabolism. Disorders of platelet number and funcCon may occur. PT and PTT can be prolonged. FDP, D-dimer, and brinogen concentraCons may be increased due to reduced clearance of plasminogen acCvators, as well as reduced synthesis of brinolyCc inhibitors. Based on results of coagulaCon tests, may be dicult to dierenCate from DIC. Look to physical exam ndings, chemistry prole changes, and liver funcCon tesCng. Causes: Platelet dysfuncCon or abnormal platelet-vessel wall interacCon due to low Hb (altered blood rheology) Clinical feature: mucocutaneous bleeding. CoagulaCon tests: normal PT and APTT; prolonged skin bleeding Cme

Haemophi lia

Von Willebran d disease

HepaDc Diseases

Uremia bleeding

Whole bleeding Dme DiagnosDc tests Platelet Count CoagulaDon Fibrinogen

Vessel wall : usually only ecchymoses Thrombocitopenia: platelets ( 80.000; mm3) / Thrombocitosis 7

PT= normal 10 -15 sec (prothrombin Cme)/ PTT= normal; 3-50 sec. (parCal thromboplasCn Cme)

Chronic BronchiDts

Lung Diseases
Asthma A. Intrinsic asthma no environmental causes can be idenCed negaCve skin test to common airborn allergens rather negaCve family history B. Extrinsic asthma atopy, geneCc predisposiCon IgE, mast cells and eosinophils response to allergens C. OccupaDonal asthma sensibilisaCon of airways to inhalant chemicals Intrinsic Asthma No allergic or (personal family) history Usually adult onset Olen follows severe respiratory illness Symptoms usually perennial More refractory to treatment Extrinsic Asthma Strong family history of allergies Usually onset at a young age Other allergic manifestaCons in paCents History of specic allergic associaCon triggers (e.g. pollen, animal dander) CorrelaCon with skin and inhalaCon responses to specic anCgens

COPD Emphysema ARDS When does it occurs? Instability of the airways = exaggerated bronchoconstrictor response to a wide variety of sCmuli 1. Acute bronchoconstricCon 2. Swelling of the airway wall 3. Chronic mucus plug formaCon 4. Airway wall remodeling

Early phase response: 30 60 minutes, allergen or irritant acCvates mast cells, inammatory mediators are released (histamine, bradykinin, leukotrienes, prostaglandins, platelet- acCvaCng-factor, chemotacCc factors, cytokines ). Intense inammaCon occurs + Bronchospasm Late phase response: 5 6 hours, it is characterized by inammaCon, eosinophils and neutrophils inltrate, mast cells release histamine and addiConal mediators, Self-perpetuaCng cycle, Lymphocytes and monocytes invade as well, Future aacks may be worse because of increased airway reacCvity that results 8 from late phase response

Chronic BronchiDs
Presence of chronic producCve cough for 3 or more months in each of 2 successive years in a paCent whom other causes of chronic cough have been excluded. Risk factors: cigaree smoke or air polluCon.

Anatomical alteraDons of lungs: Chronic inammaCon and swelling of the peripheral airways, excessive mucus producCon and accumulaCon, parCal or total mucus plugging, hyperinaCon of alveoli (air-trapping), smooth muscle constricCon of bronchial airways (mild bronchospasm)

Pathophysiology: Chronic inammaDon: Hypertrophy & hyperplasia of bronchial glands that secrete mucus. Increase number of Goblet cells (secrete mucin). Cilia are destroyed Narrowing of airway: StarCng w/ bronchi -> smaller airways: more airow resistance & work of breathing + HypovenClaCon & CO2 retenCon -> hypoxemia & hypercapnea. Bronchospasm oben occurs, as end result: Hypoxemia, hypercapnea, polycythemia (increase RBCs), cyanosis, Cor pulmonale.

Abnormal permanent enlargement of the air space distal to the terminal bronchioles. Accompanied by destrucCon of bronchioles. Abnormal distension of air spaces. Actual cause is unknown

Pathophysiology: Structural changes: HyperinaCon of alveoli, destrucCon of alveolar & alveolar-capillary walls, small airways narrow, lung elasCcity decreases. Mechanisms of structural change: ObstrucCon of small bronchioles ProteolyCc enzymes destroy alveolar Cssue ElasCn & collagen are destroyed The end result: alveoli lose elasCc recoil, then distend, & eventually blow out. Small airways collapse or narrow. HyperinaCon of alveoli (air-trapping). Decreased surface area for venClaCon There is also a permanent enlargement and deterioraCon of the air spaces distal to the terminal bronchioles; DestrucCon of pulmonary capillaries. And Bronchospasm.

EDology: cigaree smoking, geneCc predisposiCon and other chemicals irritants. ClassicaDon: Centrilobular (most common) Perilobular 9

Characterized by presence of airow obstrucCon. Caused by emphysema and/or chronic bronchiCs. Generally progressive . May be accompanied by airway hyperacCvity. May be parCally reversible

1. It is chronic 2. It is progressive 3. Mostly xed airway obstrucCon 4. Non reversible by bronchodilators 5. Exposure to noxious agent is a must 6. Two enCCes in COPD namely 7. Chronic BronchiCs 8. Emphysema

Causes: Cigaree smoking (most common and dangerous) InfecCon Heredity

Irreversible COPD Why ? Fibrosis and narrowing of the airways Loss of elasCc recoil due to alveolar destrucCon DestrucCon of alveolar support that maintains patency of small airways Reversible Bronchial Asthma AccumulaCon of inammatory cells, mucus, and exudates in bronchi Smooth muscle contracCon in peripheral and central airways Dynamic hyperinaCon during exercise

I know its enough with pictures :D 10

Respiratory Failure
Normal Values pH 7.35-7.45 PaO2 >70 mmHg PaCO2 35-45 mmHg HCO3 22-28 mmol/l Minute venClaCon = Tidal volume X Respiratory rate pH = Acidosis pH = Alkalosis PaO2 = Hypoxemia PaCO2 = Hypercapnia pH+ PaCO2 R. acidosis -- HCO3 pH+PaCO2 R.Alkalosis -- HCO3

Not a disease but a condiDon. Major threat is the inability of the lungs to meet the oxygen demands of the Cssues. Result of one or more diseases involving the lungs or other body systems. Results from inadequate gas exchange, insucient O2 transferred to the blood (Hypoxemia), inadequate CO2 removal (Hypercapnia) Clinical condiCons in which PaO2 < 60 mmHg while breathing room air or a PaCO2 > 50 mmHg Failure of oxygenaCon and carbon dioxide eliminaCon Acute or Chronic Type 1 or 2 (hypercapnic or Hypoxemic) ObstrucCve or RestricCve Causes: 1. HypovenDlaDon 2. CNS 3. Disorders of peripheral nervous system, respiratory muscles, and chest wall 4. VenDlaDon/perfusion Mismatch (V/Q) 5. Shunt 6. Diusion abnormaliDes ClassicaDon: Hypoxaemic vs. Hypercapnic Acute vs. Chronic ObstrucCve vs. restricCve Clinical Signs and Symptoms:

Compensatory mechanism, clinical signs: Respiratory compensaDon: tachypnea, use of accessory muscles, intercostal recession SympatheDc sDmulaDon: HR , BP, sweaCng Tissue hypoxia: altered mental state, HR and BP (late) Haemoglobin desaturaDon: cyanosis Type 1 = Hypoxemic RF PaO2 < 60 mmHg with normal or PaCO2 Associated with acute diseases of the lung Pulmonary edema (Cardiogenic, noncardiogenic (ARDS), pneumonia, pulmonary hemorrhage, and collapse Type 2 = Hypercapnic RF PaCO2 > 50 mmHg Hypoxemia is common Drug overdose, neuromuscular disease, chest wall deformity, COPD, and Bronchial asthma

In congesDve heart failure: Vascular congesDon: increased capillary blood volume, mild bronchoconstricCon, mild decrease in lung compliance; PaO2 normal or even increased IntersDDal edema: decreased compliance and lung volumes, worsening dyspnea, V/Q abnormality and widened A-a O2 gradient Alveolar ooding: lung units that are perfused but not venClated, shunt physiology with profound gas exchange abnormaliCes, decreased compliance and lung volumes

Hypoxemia: Dyspnea, Cyanosis, Confusion, somnolence, ts, Tachycardia, arrhythmia, Tachypnea (good sign), Use of accessory ms, Nasal aring, Recession of intercostal ms, Polycythemia, Pulmonary HTN, Corpulmonale, Rt. HF Hypercapnia: Cerebral blood ow, and CSF Pressure, Headache, Asterixis, Papilloedema, Warm extremiCes, collapsing pulse , Acidosis (respiratory, and metabolic), pH, lacCc acid


DisCncCve clinical and physiological features dene: ObstrucDve lung disease: decreased FEV1 and FEV1/VC RestricDve lung disease: decreased FEV1. Normal FEV1/ VC. Decreased Tco. Total Lung Capacity (TLC) - the total volume of the lung, the volume of air contained in the lung at the end of maximal inspiraCon Inspiratory Reserve Volume (IRV) - volume, which can be inspired beyond a resul inspiraCon Tidal Volume (TV) volume of a single breath, usually at rest FuncConal Residual Capacity (FRC) - The amount of air lel in the lungs aler a Cdal breath out, the amount of air that stays in the lungs during normal breathing Vital Capacity (VC) maximum volume which can be venClated in a single breath Inspiratory Capacity (IC) - the maximal volume that can be inspired following a normal expiraCon Expiratory Reserve Volume (ERV) volume, which can be expired beyond a resul expiraCon Residual Volume (RV) volume remaining in the lungs aler a maximum expiraCon Forced Vital Capacity (FVC) - the volume of air that can forcibly be blown out aler full inspiraCon, measured in litres Forced Expiratory Volume in 1 Second (FEV1) - the maximum volume of air that can forcibly blow out in the rst second during the FVC manoeuvre, measured in liters FEV1/FVC (FEV1%) - in healthy adults this should be approximately 7580%. In obstrucCve diseases (asthma, COPD, chronic bronchiCs, emphysema) FEV1 is decreased because of increased airway resistance to expiratory ow and the FVC may be increased (for instance by air trapping in emphysema). FEV1/FVC is decreased (<80%, olen ~45%). In restricCve diseases (such as pulmonary brosis) the FEV1 and FVC are both reduced proporConally and the FEV1/FVC value may be normal or even increased as a result of decreased lung compliance In obstrucDve diseases: LimitaCon of airow Rate of expiraDon is slowed Volume usually normal FEV1, FEV1/FVC (Asthma, COPD) In restricDve diseases: LimitaDon of lung expansion Limit to both volume & ow rate, An intersCCal disease with inammatory and broCc changes in intersCCum/interalveolar septum FEV1, FVC, FEV1/FVC normal (pneumonia, pneumothorax, brosis, pleural, cardiogenic



Renal Diseases
Glomerulopathies GlomerulonephriDs, GN, is a renal disease characterized by inammaCon of the renal glomeruli. Impairment of selecCve ltering properCes of the kidney leading to a decreased GFR Molecules normally not ltered such as consCtuents of the blood, pass into the urine and are excreted: Haematuria (especially dysmorphic red cells): red cell casts Proteinuria (may be in nephroCc range of >3.5 g/24hours) Lipiduria (glomerular permeability must be increased to allow the ltraCon of large lipoproteins) Primary conned to the kidney Secondary due to a systemic disease Clinical manifestaDons: Proteinuria asymptomaCc; Haematuria asymptomaCc; Hypertension NephroCc syndrome: gross proteinuria, hyperlipidemia NephriCc syndrome: Oliguria, Haematuria, Proteinuria, Oedema. Acute renal failure: Oliguria, loss of Kidney funcCon - within weeks Rapidly progressive renal failure: Over months and years Uremia. End stage renal failure NephriDc Syndrome: haematuria is usually macroscopic with pink or brown urine (like coca cola); oliguria may be overlooked or absent in milder cases (transient renal impairment); oedema is usually mild and is olen just peri- orbital- weight gain may be detected; +/- uid overload hypertension common and associated with raised urea and creaCnine; proteinuria is variable but usually less than in the nephroCc syndrome.

IntersDDal Vessels Diabetes problems

NephroDc Syndrome: Is not a disease but a group of signs and symptoms seen in paCents with heavy proteinuria presents with oedema proteinuria usually > 3.5g / 24hrs (>0.05g / kg / 24hrs at children) serum albumin < 30g/l other features: hyperlipidaemia, and hypercoaguable state GN categories: non-proliferaDve: lack of hypercellularity in the glomeruli; they usually cause nephroCc syndrome. ProliferaDve types: characterised by increased number of cells in the glomerulus (hypercellularity). Usually presents as a nephriCc 13 syndrome. ComplicaDons: Acute/chronic Kidney failure, HBP


lots of dierent diseases of tubules and intersCCum, very diverse aeCologies, pathogeneses and appearances, together they account for signicant numbers of cases of renal impairment. IntersDDal NephriDs, causes: InfecCon, mechanical (obstrucCon), drugs, autoimmune, metabolic (diabeCc, uric), radiaCon, neoplasCc inltraCon Bacterial infecDons: bacterial infecCon of the renal parenchyma causes intersCCal nephriCs. InfecCon without anatomical abnormality seldom produces permanent damage. ObstrucCon (stones, prostate etc) in combinaCon with infecCon can cause progressive disease. Tuberculosis causes extensive destrucCon because of granulomas, brosis and caseaCon. PyelonephriDs: Commonly bacterial (Gram negaCve: E.coli, Proteus, Klebsiella, Pseudomonas, Enterobacter) Risk factors: Anomalies, InstrumentaCon, ObstrucCon, bladder dysfuncCon, reux, Pregnancy Symptoms: pain at the costovertebral angle, fever, chills, malaise, Urine: pyuria, bacteria, Dysuria Natural history: Self-limiCng, recurrent, chronic PolycysDc Renal Disease Adult: Autosomal dominant. Huge kidneys full of cysts. Usually no symptoms unCl 30 years. Associated with brain aneurysms. Childhood: Autosomal recessive. Numerous small corCcal cysts. Associated with liver cysts PaCents olen die in infancy

Acute tubular necrosis (ATN): most important cause of acute renal failure; characterized by acute destrucCon of tubular epithelial cells; most commonly secondary to ischaemia, but can also be due to direct toxic cell damage; potenCally reversible, since tubular cells can regenerate (if given Cme). Types: 1. Ischemic: State of hypoperfusion (shock and reducCon in intrarenal blood ow ) 2. Nephrotoxic (heavy metals, solvents, drugs, anCbioCcs, NSAIDs, diureCcs, medium contrast for radiology, pesCcides) In both types we will nd: tubular cell degeneraCon and death, tubular casts of dead cells & debris, intersCCal oedema & secondary inammaCon, pale swollen kidneys, reversible lesion, destrucCon of tubular epithelium, acute suppression of renal funcCon (urine output > 400ml/day)

Gout, Uric Acid and Renal Disease uric acid calculi, parenchymal deposits of uric acid and tubular obstrucCon with urate can cause renal damage an elevated plasma uric acid does not in itself seem to cause renal damage 1/4 of paCents with gout get uric acid stones 1/4 of paCents with uric acid stones will have gout acute nephropathy with overproducCon of uric acid and kidney obstrucCon with uric acid crystals; can occur following treatment of malignant diseases with cytotoxics, heat stroke or status epilepCcus; treat with uids and prophylaxis with allopurinol; role of uric acid in chronic renal failure is disputed, but does occur with some familial disorders;

Autosomal Dominant PolycysDc Kidney Disease: accounts for 7-10% of people on dialysis. 50% of suerers have renal failure by age 60. Cysts may occur in liver and pancreas but do not usually give problems 14

Renal Failure

Acute: sudden onset, rapid reducCon in urine output. Usually reversible. Tubular cell death and regeneraCon Chronic: Progressive. Not reversible. Nephron loss (75% of funcCon can be lost before its noCceable)


Inability of kidney to maintain homeostasis leading to a buildup of nitrogenous wastes Dierent to renal insuciency where kidney funcCon is deranged but can sCll support life Occurs over hours/days Lab deniCon 1. Increase in baseline creaCnine of more than 50% 2. Decrease in creaCnine clearance of more than 50% 3. DeterioraCon in renal funcCon requiring dialysis Anuria no urine output or less than 100mls/24 hours Oliguria - <500mls urine output/24 hours or <20mls/hour Polyuria - >2.5L/24 hours Sudden interrupDon of kidney funcDon resulCng from: - reduced circulaCon: Pre-renal = 55% - disease of the renal Cssue: Renal parenchymal (intrinsic)= 40% - obstrucCon: Post-renal = 5-15% Results in retenDon of toxins, uids, and end products of metabolism Usually reversible with medical treatment May progress to end stage renal disease, uremic syndrome, and death without treatment Types: Pre-Renal or funcConal (hypovolemia, shock, blood loss, embolism, ascites or burns, CV disorder, etc.) Intrarenal or intrinsic/structural (nephrotoxic agents, infecCons, ischemia, etc.) Postrenal or obstrucCve (stones, blood clots, etc.)

Results from gradual, progressive loss of renal funcCon. Occasionally results from rapid progression of acute renal failure. Symptoms occur when 75% of the nephrons are lost, but considered chronic if 90-95% loss of funcCon. Dialysis is necessary D/T accumulaCon of uremic toxins, which produce changes in major organs. Chronic renal failure, or ESRD, is a progressive and irreversible deterioraCon in renal funcCon in which the bodys ability to maintain metabolic and uid and electrolyte balance fails, resulCng in retenCon of urea and other nitrogenous wastes in the blood. Uremia develops and adversely aects every system in the body. ESRD occurs when there is less than 10% nephron funcCon remaining. All of the normal regulatory, excretory, and hormonal funcCons of the kidney are severely impaired. Is stated as the presence of GFR <60 mL/min/1.73 m2 for three months, with or without other signs of kidney damage as described above. Triggers also low GFR, Na and K retenCon, metabolic acidosis and anemia. Causes: DiabeCc Nephropathy Hypertension GlomerulonephriCs HIV nephropathy Reux nephropathy in children PolycysCc kidney disease Kidney infecCons & obstrucCons 15


It is yellowish discoloraCon of: skin, mucous membranes, sclera; due to excess plasma bilirubin

The dierenCal diagnosis for yellowing of the skin is limited. InaddiCon to jaundice, it includes Carotenoderma, the use of the drug, Quinacrine, excessive exposure to phenols. Is not a disease but rather a sign that can occur in many dierent diseases. Normal ndings for bilirubin is 5-17 m mol/l, while clinically obvious results are: 50 mmol/l (2.5mg/dl). Bilirubin is a bile pigment, lipid soluble and is a product of heme metabolism (check the HEME metabolism picture ->) 75% is derived from RBCs. In normal adults this results in a daily load of 250-300 mg of bilirubin. Normal plasma concentraCons are less then 1 mg/dL

Interferences at any one of the points of bilirubin processing described above can lead to a condiCon known as HYPERBILIRUBINEMIA. Causes: In rst 3 -> unconjugated N. Increased bilirubin producCon Reduced bilirubin uptake by hepaCc cells Disrupted intracellular conjugaCon Last 2 -> Conjugated Disrupted secreCon of bilirubin into bile canaliculi Intra/extra-hepaCc bile duct obstrucCon

Pre-HepaDc (hemolyDc): excess producCon of bilirubin (beyond the livers ability to conjugate it) HepaDc: a generalized liver (hepatocyte) dysfuncCon Post-HepaDc (obstrucDve): by an obstrucCon of the biliary tree 16

Pancreas Problems

What is Sphincter of Oddi DysfuncDon? The sphincter of Oddi has three major funcCons: 1) regulaCon of bile and pancreaCc ow into the duodenum, 2) diversion of hepaCc bile into the gallbladder, and 3) the prevenCon of reux of duodenal contents into the pancreaCcobiliary tract. The major physiologic role of the sphincter is the regulaCon of the ow of bile and pancreaCc juice. There are two types of sphincter of Oddi dysfuncCon: 1) papillary stenosis and 2) sphincter of Oddi dyskinesia. Papillary stenosis is a xed anatomic narrowing of the sphincter, olen due to brosis. Sphincter of Oddi dyskinesia refers to a variety of manometric abnormaliCes of the sphincter of Oddi


When the acCvaCon of digesCve proenzymes occurs in pancreaCc duct system or aciner cells, the inammaCon is the result. Oedema or obstrucCon of ampulla of Vater resulCng in reexes Of bile into pancreaCc duct or to acinar cells. Pancreas shows edema & necrosis. (10%-30% mortality rate). The release of digesCve enzymes lead to fat necrosis in the pancreas &peritoneal cavity. ACUTE CHRONIC

Pathophysiology: insult leads to leakage of pancreaCc enzymes into pancreaCc and peripancreaCc Cssue leading to acute inammatory reacCon, Steps: STAGE 1: PancreaCc Injury (Edema, InammaCon) STAGE 2: Local Eects (retroperitoneal edema, Ileus) STAGE 3: Systemic ComplicaCons (Hypotension/shock, Metabolic disturbances, Sepsis/organ failure) AutodigesDon theory: AcCvated enzymes digest cellular membranes, cause proteolysis, edema, intersCCal hemorrhage, vascular damage, coagulaCon & fat necrosis, parenchymal cell necrosis LiberaCon of bradykinin pepCdes, increased vascular permeability, and edema with profound eects on many organs, esp. the lungs SIRS, ARDS, MulCorgan Failure, other distant eects

Pathophysiology: irreversible parenchymal destrucCon leading to pancreaCc dysfuncCon. Persistent, recurrent episodes of severe pain. Anorexia, nausea. ConsCpaCon, atulence. Steatorrhea. Diabetes. Causes: #1- eCology is chronic EtOH abuse (90%) Gallstones Hyperparathyroidism Congenital malformaCon (pancreas divisum) Idiopathic ComplicaDons: Shock & renal failure, hypo Ca, hypoalbuminemia, hyperglucemia, hypoxia. Others are exocrine insuciency (steatorrhea) and endocrine insuciency may result from islet cell destrucCon which leads to diabetes 17

A portal system of veins is one which begins and also ends in capillaries. The portal venous branches ramify in an arterial like paern and end in dilated channels called sinusoids, which are equivalent to systemic capillaries. From here blood drains into the hepaCc venous system. The normal portal pressure is 5-7 mmHg (8-12 cm of water). Portal hypertension is present when the portal vein pressure exceeds 12 mmHg Portal hypertension is a high blood pressure in the portal vein and its tributaries (portal venous system). It is dened as a portal pressure gradient (the dierence in pressure between the portal vein and the hepaCc veins) of 5 mm Hg or greater. PRESSURE ABOVE 40 mm Hg. Causes: 1. INCREASED RESISTENCE: Pre-hepaCc (pre-sinusoid): portal vein obstrucCon, congenital, thrombosis, extrinsic Intra-hepaCc (sinusoid): liver cirrhosis, bilharzial periportal brosis Post-hepaCc (post-sinusoid): Budd-Chiari syndrome (hepaCc vein thrombosis) , Veno-occlusive disease and cardiac problems 2. INCREASED BLOOD FLOW: Arterial-portal venous stula Increased splenic ow: BanCs syndrome or splenomegaly

Portal CirculaDon


Porto-systemic collaterals (caput medusae, oesophageal varices, haemorrhoids). Splenomegaly (congesCve).CongesCon of the whole GIT. Bleeding varices. Ascites. InvesDgaDons: Assessment of liver funcCon tests: (a) Hypoalbuminaemia = the liver is the only site of albumin synthesis. (b) ALT & AST are moderately raised. (c) Prothrombin Cme and concentraCon are disturbed = this test is the most sensiCve liver funcCon. DetecCon of oesophageal varices by opCc bre endoscopy or by baritate swallow (radiology) or duplex technique. DetecCon of splenic sequestraCon and hypersplenism: blood analysis, bone marrow examinaCon and radioacCve isotopes studies Diagnosis of the aeCology of liver disease is performed by immunological test (hepaCCs) or liver biopsy Describes the condiCon of pathologic uid collecCon within the abdominal cavity. Can develops for Increased hydrostaCc pressure, Decreased colloid osmoCc pressure, Increase permeability of peritoneal capillaries, Leakage of uid into the peritoneal cavity or miscellaneous causes. In CirrhoCc ascites it develops because of the portal hypertension, the lymph formaCon, renal abnormaliCes with Na retenCon and water retenCon. Also renal vasoconstricCon increase the probability of ascites (late phenomena). The Serum-ascites albumin gradient (SAAG) is beer discriminant than older measures (transudate versus exudate) for the causes of ascites. ClassicaDon: a. A high gradient ( 1.1 g/dL) indicates the ascites is due to portal hypertension. b. A low gradient (< 1.1 g/dL) indicates ascites of non-portal hypertensive eCology.



Most common mechanism: short circuit that forms between two pathways that are either anatomically or funcConally disCnct Typically: Path 1: Slow conducCon, short refractory period Path 2: Rapid conducCon, long refractory period


Trigger AcDvity

Is a benign type of automaCcity problem that aects only a small region of atrial or ventricular cells. 3% of PVCs

Is like a domino eect where the arrhythmia is due to the preceding beat. Delayed aler- depolarizaCons arise during the resCng phase of the last beat and may be the cause of digitalis-induced arrhythmias. Early aler-depolarizaCons arise during the plateau phase or the repolarizaCon phase of the last beat and may be the cause of torsades de pointes

Heart cells other than those of the SA node depolarize faster than SA node cells, and take control as the cardiac pacemaker. Factors that enhance automaCcity include: SANS, PANS, CO2, O2, H+, stretch, hypokalemia and hypocalcaemia. Examples: Ectopic atrial tachycardia or mulCfocal tachycardia in paCents with chronic lung disease OR ventricular ectopy aler MI

What is an arrhythmia? Any abnormality of the cardiac rhythm is called a cardiac arrhythmia. AbnormaliCes of electrical rhythm: generaCng rhythm, conducCon of the electricity . There are two main types of arrhythmia: Bradycardias: the heart rate is slow (< 60 bpm) Tachycardias: the heart rate is fast (> 100 bpm) Common names per region: Atrial: AF, Paroxs. Supra-Ventricular-Tachycardias or SVT ( AVNRT, AVRT (WPW), MulCfocal atrial tachycardia) Ventricular: VT, VF, Torsades Bradyarrythmia: MedicaCon, AV block, SSS Clinical ManifestaDons: PalpitaCons, Syncope, If going fast enough, can precipitate cardiac ischaemia and chest pain, Cardiac failure, Decreased level of consciousness, Hypoperfusion of all organs, Cardiac arrest. ***I has not insisted on each subtype of AR and ecg ndings, you can nd most of them in my previous review from 1st semester


Primary (idiopathic) is a disease of unknown eCology that principally aects the myocardium leading to LV dilaCon and systolic dysfuncCon. Secondary causes include ischemia, alcoholic, peripartum, post-infecCous, viral. Most common of the cardiomyopathies. DilaCon and impaired contracCon of ventricles: Reduced systolic funcCon with or without heart failure Characterized by myocyte damage MulCple eCologies with similar resultant pathophysiology


Most rare form of cardiomyopathy. Characterized by broadipose replacement of segments of the free wall of the right ventricle. Exam usually normal. EKG- RBBB may be present. Echo-necessary for diagnosis. Regional wall moCon/funcCon is reduced. Familial and progressive. Predominately found in young adults. Ventricular arrhythmias: cause of young adult sudden death

Are a heterogeneous group of diseases of the myocardium, associated with mechanical &/or electrical dysfuncCon

Arrhythmogenic / others


GeneCc disease characterized by hypertrophy of the lel ventricle with marked variable clinical manifestaCons morphologic and hemodynamic abnormaliCes. Most common cause of death in young people. The magnitude of lel ventricular hypertrophy is directly correlated to the risk of sudden cardiac death (SCD) . Young pts with extreme hypertrophy and few or no symptoms are at substanCal long-term risk of SCD. Vigorous systolic funcCon, but impaired diastolic funcCon, impaired relaxaCon of ventricles, elevated diastolic pressures.

Least common type of cardiomyopathy. Increased sCness of the myocardium -> impaired diastolic lling. Ventricular volumes are usually normal or reduced. Wall thickness is normal or mildly increased . Systolic funcCon is typically preserved. Usually dilated atria.. Hallmark: abnormal diastolic funcCon Rigid ventricular wall with impaired ventricular lling Bear some funcConal resemblance to constricCve pericardiCs Importance lies in its dierenCaCon from operable constricCve pericardiCs Characterized by: impaired ventricular lling due to an abnormally sC (rigid) ventricle, normal systolic funcCon (early on in disease), intraventricular pressure rises precipitously with small increases in volume 20


Valve Stenosis: obstrucCon to valve ow during that phase of the cardiac cycle when the valve is normally open. Hemodynamic hallmark -pressure gradient ~ ow// VA Valve RegurgitaDon: Insuciency, Incompetence, Inadequate valve closureback leakage A single valve can be both stenoCc and regurgitant; but both lesions cannot be severe!! CombinaCons of valve lesions can coexist

Mitral Stenosis

Limited ow into the LV has 3 major sequale: ElevaCon of Lt. Atrial pressure, Secondary RV pressure overload, hemopCsy, Reduced LV ejecCon performance.Due to diminished preload.Tachycardic response to compensate to decreased SV worsens the transmitral gradient. EDology: rheumaDc, infecCve endocardiCs, mitral calcicaCon. Natural history: Progressive, lifelong disease, Usually slow & stable in the early years.Progressive acceleraCon in the later years 20-40 year latency from rheumaCc fever to symptom onset. AddiConal 10 years before disabling symptoms Mortality: Due to progressive pulmonary congesCon, infecCon, and thromboembolism Pure Volume Overload. Compensatory Mechanisms: Lel atrial enlargement, LVH and increased contracClity. EDology: Valvular-leaets (Myxomatous MV Disease, RheumaCc endocardiCs, congenital-clels); Chordae defects; Annulus calcicaCon; Papillary Muscles problems; LV dilataCon & funcConal regurgitaCon or Trauma. Chronic MR deniDon: Backow of blood from the LV to the LA during systole, a Mild (physiological) MR is seen in 80% of normal individuals. Is a narrowing of the aorCc valve opening caused by the failure of the valve leaets to open normally. Concentric LVH then develops due to an increase in LV pressure. Thickening and sCening of the LV in the face of increasing obstrucCon results in increased LVEDP. Result = LAH and diastolic dysfuncCon. In signicant Ao. stenosis, the cardiac output may be fairly well maintained at rest but fails to augment with exercise. EDology: congenital, rheumaCc, degeneraCve or calcic.

Mitral Regurgita Don

AorDc stenosis

AorDc Regurgita Don

DeniDon: Leakage of blood from aorta into LV during diastole due to ineecCve coaptaCon of the aorCc cusps. Combined pressure AND volume overload. Compensatory Mechanisms: LV dilaCon, LVH. Progressive dilaCon leads to heart failure. EDology: InfecCve endocardiCs (majority of cases), AorCc DissecCon of the root of the aorta, Trauma. There is an acute and a chronic subtype.

HTN, ECG and Ischemic heart disease are not developed in this review. You Beloved Colleague May the Force Be With You Alessandro MoIa, UVVG, 3rd year