Acute Respiratory failure

 General criteria used to define acute respiratory failure:

 Hypoxia (PaO2 < 60 mm hg and PaCO2 > 50 mm hg)
 Hypercapnia (partial pressure of CO2 (PCO2)> 59 mm hg.
 Classification:
 Hypoxemic RF:
 PaCO2 that is either low or normal when O2 saturation is <90% despite FiO2 >
0.6
 ARDS
 Severe pneumonia
 Pulmonary edema
 Hypercarbic (ventilatory) RF:
 Decrease in minute ventilation or an increase in physiologic dead space lead to
CO2 retention and eventually results in hypoxemia
 May be caused by:
 COPD
 Asthma
 Severe bronchitis
 Pathophysiology:
 Interpulmonary shunting:
 Little or no ventilation in perfused areas due to collapsed or fluid-filled alveoli
 Hypoxia due to shunt is not responsive to supplemental oxygen
 Clinical features:
 Symptoms
 Dyspnea-1 symptom
st

 Cough may or may not be present

 Signs
 Inability to speak in complete sentences
 Use of accessory muscles of respiration
 Tachypnea, tachycardia
 Cyanosis
 Impaired mentation (due to fatigue or hypercapnia)

1
 Arthropathy
Danish + slides

inflammatory arthralgia
hotness Mild hotness
Swelling
redness
Loss of function
Diffuse pain present at rest and with normal use
Nocturnal pain
Morning stiffness (30-60min) Morning stiffness < 15 min
Fatigue is common occurs by early afternoon after stiffness Fatigue is uncommon
subsided
Pain is worse by inactivity Pain worse by activity
 Arthritis:
 Associated symptoms:
 Fever  infection or post infection
 Rashes  erythema nodosum, psoriatic plaque, erythema migrans, erythema
marginatum (rheumatic fever), butterfly malar rash.
 Diarrhea, abdominal pain, urethral discharge, low back pain, uveitis  reactive
arthritis.
 Mono
 1# septic
 2# crystal induced
 Oligo
 2-4 joints
 1# crystal
 2# septic
 poly
 > 5 joints
 1# crystal
 2# infection  parvovirus.
 3# HBV, HCV, HIV.
 4# dengue fever
 Osteoarthritis  bilateral knees
 Gout’s pain is alternating
 Gout comes with fever
 Most common cause of chronic inflammatory polyarthritis that involves small and large
joints bilaterally and symmetrically in upper and lower extremities is  RA
 Distal interphalangeal joints:
 Psoriatic arthritis
 Gouty arthritis
 Osteoarthritis
 Multicentric reticulohistocytosis

2
  1st metatarsophalangeal joint  gouty arthritis

 Investigation:
 CBC
 LFT
 Kidney function
 ESR
 C-reactive protein
 If septic  blood culture
 Pattern of joint involved
 Additive
 Most common
 Rheumatoid arthritis present like this
 Recruitment of new joints while affected ones remain active
 Migratory
 Symptoms being present in certain joints for a few days and the remit, only to
appear in other joints.
 Caused by
 Rheumatic fever
 Gonococcal arthritis
 Lyme disease
 Acute leukemia of childhood
 Intermittent
 Repetitive attacks of acute poly-arthritis with complete remission between
attacks
 Caused by:
 Crystal arthritis
 RA
 Still’s disease
 SLE
 Sarcoidosis
 Palindromic rheumatism
 Familial Mediterranean fever
 Whipple associated arthritis
 Seronegative spondylarthropathy
 Young adult male
 Ankylosing spondylitis
 Reactive arthritis
 HIV
 HCV arthritis
 Young adult female
 Gonococcal arthritis
 Parvovirus
 Rubella arthritis
 SLE

3
Asthma
Davidson + osmosis + step up medicine

 General characteristics:
 Defined by following triad
 Airway inflammation
 Airway hyperresponsiveness
 Reversible airflow obstruction
 Asthma can begin at any age
 chronic, reversible airway inflammation characterized by periodic attacks of wheezing, SOB, chest
tightness, and coughing
 peak flow meters are useful in the office and at home for monitoring
 Extrinsic vs intrinsic asthma
 Extrinsic asthma (most cases)
 Patients are atopic i.e., produce immunoglobulin E (IgE) to environmental
antigens. May be associated with eczema and hay fever.
 Patients become asthmatic at a young age
 Intrinsic asthma – not related to atopy or environmental triggers
 Triggers include pollens, house dust, molds, cockroaches, cats, dogs, cold air, viral
infections, tobacco smoke, medication (b-blockers, aspirin), and exercise.
 Chronic inflammatory disorder of airways, smooth muscle spasm(reversible) + increased
mucous secretion narrow airway. Is a type of obstructive lung disease. Over years 
edema scarring and fibrosis  thickened wall basement.
 Symptoms include dyspnea + chest tightness + cough + wheezing + symptoms free
period.
 Sputum  has curschmann spirals  mucous plugs  casts from small bronchi.
 Asthma is classified according to 1. Amount of obstruction: a. FEV1. b. PEFR (peak
expiratory flow rate., 2. Frequency if symptoms: a. night time b. Early morning
 Types: 1. Intermittent. 2. Mild persistent. 3. Moderate persistent. 4. Severe persistent.
 Affects 300 million people.
 Pathophysiology: common example of allergens includes dust mites, pets, pests, fungi.
Followed by Broncho constrictor response. In case of Aspirin-sensitive asthma 
ingestion of salicylates or NSAID  inhibit cyclooxygenase  shunting metabolism of
arachidonic acid through lipoxygenase pathway  asthmogenic cysteinyl leukotrienes.
In exercise induced asthma  hyperventilation + heat loss from mucosa of lung 
water loss from peri cellular lining fluid of respiratory mucosa  triggers mediator
release.
 Clinical picture:
 Typical symptoms include recurrent episodes of wheezing, chest tightness,
breathlessness, cough.
 Classical precipitants include exercise, particularly In cold weather, exposure to
airborne allergens or pollutants, viral URTI.
 Little to find on examination.
 Inspection for nasal polyp and eczema should be performed. Patients with mild
intermittent asthma are usually asymptomatic between exacerbations. Asthma
characteristically displays a diurnal pattern with symptoms, lung function being

4
 worse in early morning, particularly when poorly controlled. Symptoms such as
cough wheeze disturb sleep and have led to term nocturnal asthma. Particular
enquiry should be made about potential allergens. Can be triggered by medication 1.
Aspirin 2. Oral contraceptive pills 3. Cholinergic agents 4. Beta-blockers. Severe form
of asthma is more common in women.
 Symptoms are typically worse at night
 Investigation:
 Peak flow meter
 CXR if diagnosis in doubt to rule out pneumonia, pneumothorax.
 Diagnosis:
 based on history.
 By using spirometer, to measure FEV1, VC. Patients should be instructed to record
peak flow reading after rising in morning and before bed. > 20% diurnal variation of >
3 days in a week for 2 weeks on PEF diary. FEV1 > 15% decrease after 6 min of
exercise. FEV1 > 15% increase following administration of bronchodilator/trial of
corticosteroids.
Bronchiectasis
Step-up medicine

 General characteristics:
 Permanent, abnormal dilation and destruction of bronchial walls. Cilia are damaged;
onset is usually in childhood.
 Less common today, because modern Abx are used for respiratory infections.
 Causes:
 Cystic fibrosis is most common cause of bronchiectasis
 Infection, humoral immunodeficiency (abnormal lung defense), airway obstruction
 Clinical features:
 Chronic cough with large amounts of mucopurulent, foul-smelling sputum
 Dyspnea
 Hemoptysis – due to rupture of blood vessels near bronchial wall surface; usually
mild and self – limited, but sometimes can be brisk and present as an emergency
 Recurrent or persistent pneumonia
 Diagnosis:
 CT scan
Cirrhosis

1. Is a chronic liver diseased characterized by fibrosis, disruption of liver architecture,

and widespread nodules in the liver
2. Irreversible when advanced.
3. Distortion of liver anatomy cause two major events
a. Decreased blood flow through the liver with subsequent hypertension is
portal circulation including ascites, peripheral edema, splenomegaly, and
varicosity of veins
b. Hepatocellular failure  impairemnet of biochemical functions such as
decreased albumin synthesis, and decreased clotting factor synthesis
5
 c. Hepatic functional reserve
i. Child’s classification
1. Measure disease severity
4. Causes:
a. Alcoholic liver disease – most common
i. Range of conditions from fatty liver (reversible, due to acute
ingestion) to cirrhosis (irreversible)
ii. Chronic hepatisis B and C infections – next common cause
iii. Drugs (acetaminophen toxicity, methotrexate)
iv. Autoimmune hepatitis
v. 1ry biliary cirrhosis
5. Complications
a. Portal HTN
i. Bleeding (hematemesis, melena, hematochezia) 2ry to esophageal
varices is the most life threatening complication of portal HTN
b. Varices
i. Esophageal/gastric
1. Patients with cirrhosis should be evaluated to document
presence of varices and risk of hemorrhage
2. Clinical features  massive hematemesis, melena, and
exacerbation of hepatic encephalopathy
3. Rectal hemorrhoids
4. Caput medusa (distention of abdominal wall veins)
c. Ascites
i. Fluid in the peritoneal cavity due to portal HTN and
hypoalbuminemia. Ascites Is the most common complication of
cirrhosis
ii. Clinical features: abdominal distention, shifting dullness and fluid
wave.
iii. Diagnostic paracentesis determines whether ascites is due to portal
HTN ir another pe=rocess
d. Hepatic encephalopathy
i. Toxic metabolites (ammonia)
ii. Occurs in 50% of a;; cases of cirrhosis
6. Differential diagnosis of ascites:
a. Cirrhosis, portal HTN
b. CHF
c. Chronic renal disease
d. Massive fluid overload
e. TB peritonitis
f. Malignancy
g. Hypoalbuminemia

Colorectal cancer

 Major are adenocarcinomas.

6
 Screening :
 Fecal occult blood testing has poor sensitivity and specificity
 Digital rectal examination: only about 10% of tumors are palpable by rectal
examination
 Colonoscopy
 Most sensitive and specific test
 Risk factors:
 Age – everyone over the age of 59 years is at increased risk
 Adenomatous polyps
 Premalignant lesions, but most do not develop into cancer
 Callous adenomas have higher malignant potential than tubular adenomas
 The larger the size and the greater the number of polyps, the higher the risk of
cancer
 IBD
 Both UC, and crohn’s disease pose an increased risk for colorectal cancer, but US
poses a greater risk
 Family history
 Multiple 1st degree relatives with CRC
 Any 1st degree relative diagnosed with CRC or adenoma under the age of 60
 Dietary factors – high fat, low fiber diets associated with a higher risk for CRC
 Major polyps syndrome
 Familial adenomatous polyposis
 AD. Hundreds of adenomatous polyps in the colon. The colon is always
involved and the duodenum is involved in 90% of cases
 Risk of CRC is 100% by 3rd or 4th decade of life
 Clinical features:
 Most symptoms have melena or hematochezia, abdominal pain, change in bowel
habits, or unexplained iron deficiency anemia
 Abdominal pain. CRC is the most common cause of large bowel obstruction in adults.
 Weight loss
 Blood in stool
 May be asymptomatic
COPD
Davidson + osmosis

 General characteristics:
o Two types of COPD: chronic bronchitis, emphysema
 Chronic bronchitis:
 Clinical diagnosis
 Chronic cough productive of sputum for at least 3 months
per year for at least 2 consecutive years
 Emphysema:
 Pathologic diagnosis

7
  Permanent enlargement of air spaces distal to terminal
bronchioles due to destruction of alveolar wall
 Emphysema and chronic bronchitis often coexist
th
o 4 leading cause of death in US.
o Risk factors:
 Tobacco smoke 90% of COPD
 Alpha-1-antitrypsin deficiency – risk is even worse in combination
with smoking
 Environmental factors: e.g. 2nd hand smoke
 Chronic asthma is an independent risk factor
 Preventable and treatable disease characterized by persistent airflow limitation
usually progressive.
 Related diagnoses include chronic bronchitis (cough and sputum on most days
for at least 3 months, in each of 2 consecutive years) and emphysema (abnormal
permanent enlargement of airspace distal to terminal bronchioles accompanied
by destruction of their walls and without obvious fibrosis) + weight loss and
skeletal muscle dysfunction.

 Commonly associated comorbid conditions include cardiovascular

disease, cerebrovascular disease, the metabolic syndrome, osteoporosis,
depression and lung cancer.

 related to the prevalence of tobacco smoking and the use of biomass fuels

 greatest in Asian, and African countries as a result of increased tobacco

consumption.

 Individual susceptibility factors are important.

 Pathophysiology: presence of airflow limitation combined with premature airway closure

 gas trapping and hyperinflation, reducing pulmonary and chest wall compliance.
Placing the respiratory muscles at a mechanical disadvantage. The work of breathing
increased, first on exercise but then as the disease advances, at rest.

 Chronic bronchitis:

 Excess mucus narrows the airways, patients often have a productive cough

 Inflammation and scarring in airways, enlargement in mucous glands and smooth

muscle hyperplasia  obstruction

 Emphysema:

 Destruction of alveolar walls is due to relative excess in protease or deficiency of

antiprotease (alpha-1-antitrypsin) activity in lung.

 Elastase is released from PMNs and macrophages and digests human lung.

8
  Tobacco smoke increases the number of activated PMNs and macrophages, inhibit
alpha-1-antitrypsin and increases oxidative stress on the lung by free radicals.

 Clinical features:

 COPD should be suspected in any patient > 40 years old who presents with symptoms
of chronic bronchitis and/or breathlessness.

 Differential diagnosis  chronic asthma, TB, bronchiectasis, congestive cardiac

failure.

 Breathlessness usually precipitates the presentation to health care.

 Enquiry should be made about the presence of edema, which may be seen for the 1st
time during an exacerbation and morning headache which may suggest hypercapnia.
May develop edema and 2ry polycythemia.

 Symptoms:

 Cough, sputum production and dyspnea (on exertion or at rest). Exertional

dyspnea is the most common early symptom of COPD.

 Signs:

 Prolonged Forced expiratory time

 End-expiratory wheeze on forced expiration, decreased breath sounds and/or

respiratory crackles

 Cyanosis

 Use of accessory respiratory muscles

 Hyperresonance on percussion

 Tachypnea, tachycardia

 Investigation:

 a chest x-ray

 hyperinflation, flattened diaphragm, enlarged retrosternal space

 Blood count is useful to exclude anemia or polycythemia, alpha 1 antiproteinase

should be assayed.

 Airflow by spirometry FEV1/FVC is < 70%. Emphysema is suggested by a low gas

transfer value.

9
  Increased total lung capacity, residual volume, and functional reserve capacity
(indicating air trapping) but decreased vital capacity.

 Chronic bronchitis: V.C.  localized to one area of lung  effective but to large
proportion of lung  high pulmonary vascular resistance  pulmonary hypertension 
more work on right heart side  right side hypertrophy  right side HF (cor pulmonale).
Risk factors: air pollutants ( S2, NO2 ). Dust & silica. Genetic  family history. Airway
obstructed  trapped air. Exposure to irritants & chemicals  hypertrophy &
hyperplasia of bronchial mucinous glands (main bronchi) & goblet cells (bronchioles) 
cilia short + less mobile (because of mucous). Signs and symptoms  wheeze, crackles,
hypoxemia, hypercapnia. Hight PCO2, low PO2.

 Emphysema: inflammation  protease (elastase, collagenase) breakdown structural

proteins (collagen, elastin) alveoli collapse  usually upper lobes of lung  acinar
emphysema. If associated with alpha1-antitrypsin where protease inhibitor is lacking that
protect against unintended damage  panacinar emphysema, which affects lower lobes
of the lung.

CVS examination
Telly

 To help determine the cause of chest pain. It is imp to ascertain the duration, location,
quality, and precipitating and aggravating factors, as well as means of relief and
accompanying symptoms.
 In angina the pain is usually central rather than left sided. It may radiate to the jaw or to
the arms. Very rarely to umbilicus.
 Ischemic chest pain is usually unaffected by respiration. Pain present for more than half
an hour is more likely to be due to MI than angina. Associated symptoms of MI include
dyspnea, sweating, anxiety, nausea, and faintness.
 Chest pain made worse by inspiration is called pleuritic pain  due to pleurisy or
pericarditis.
 Pain due to dissecting aneurysm is very severe may be described as tearing. And radiates
to the back. people with history of HTN or connective tissue disorders such as Marfan’s
syndrome or EDS are at high risk.
 Dyspnea: defined as an unexpected awareness of breathing. It occurs whenever the
work of breathing is excessive.
 Orthopnea: dyspnea that develops when a patient is supine. Patients with severe
orthopnea spend night sitting up in a chair or propped up on numerous pillow in bed.
 Paroxysmal nocturnal dyspnea (PND): is severe dyspnea that wakes the patient from
sleep so they are forced to get up gasping for breath. This occurs because of sudden
failure of left ventricular output.
 Ankle swelling: some patients present with bilateral ankle swelling due to edema from
cardiac failure. Usually symmetrical and worst in the evenings with improvement during
the night.
 Palpitation: unexpected awareness of the heartbeat. Ask Whether the palpitations are
slow or fast, regular or irregular, and how long they last.

10
 Syncope: is a transient loss of consciousness resulting from cerebral anoxia. Presyncope
is a transient sensation of weakness without loss of consciousness.
 Fatigue: common symptom of cardiac failure. Other causes of fatigue  lack of sleep,
depression and anaemia.
 The CVS examination :
Cystic fibrosis
Davidson + step up medicine

 The most common fatal genetic disease in Caucasians, with Autosomal recessive
inheritance, a carrier rate 1 in 25 and an incidence of about 1 in 2500 live births
 Defect in chloride channel protein causes impaired chloride and water transport 
excessively thick, viscous secretions in respiratory tract, exocrine pancreas, sweat
glands, intestines, and GIT. The genetic defect causes increased sodium and chloride
content in sweat and increased resorption of sodium and water from respiratory
epithelium. Relative dehydration of the airway epithelium is thought to predispose to
chronic bacterial infection and ciliary dysfunction  bronchiectasis.
 Typically results in obstructive lung disease with chronic pulmonary infections
(frequently Pseudomonas), pancreatic insufficiency, and other GI complications
 The clinical picture (bowel obstruction, failure to thrive, steatorrhea and/or chest
symptoms in a young child. Supported by sweat electrolyte testing and genotyping
 Clinical features:
 The lungs are macroscopically normal at birth, but bronchial inflammation and
infections usually lead to bronchiectasis in childhood. At this stage the lungs
commonly infected with staph. Aureus. In adulthood many patients become
colonized with Pseudomonad Aeroginosa.
 Respiratory
 Spontaneous pneumothorax
 Hemoptysis
 Nasal polyp
 Respiratory failure
 Lobar collapse due to secretions
 GI
 Malabsorption and steatorrhea
 Distal intestinal obstruction syndrome
 Gallstones
 Biliary cirrhosis and portal hypertension
 Others
 Diabetes (25% of adults)
 Delayed puberty
 Male infertility
 Stress incontinence due to repeated forced cough
 Psychosocial problems
 Osteoporosis
 Arthropathy
 Cutaneous vasculitis

11
Diabetes Mellitus
slides
 What is diabetes?
o FBG >126 mg/dl, 2h PG >200mg/dl, A1c >6.5%
 Who to screen for diabetes?
o BMI >25 or >23 if Asian
o 1st degree relative with diabetes
o Hx of CVD, hypertension
o HDL <35
o Physical inactivity
o A1c >5.7
o Women with gestational diabetes
o >45 YO
 Classification of diabetes:
o T1DM :
 Autoimmune b-cell destruction  absolute insulin deficiency
o T2DM:
 Progressive loss of B-cell insulin secretion + insulin resistance
o GDM:
 Diabetes diagnosed in 2nd-3rd trimesters of pregnancy that wasn’t
overt diabetes prior to gastation
 Complication of diabetes millitus:
o Acute:
 DKA
 Hyperosmolar state
 Hypoglycemia
o Chronic:
 Microvascular:
 Nephropathy (yearly checkup)
 Neuropathy (yearly checkup)
 Retinopathy
 Macrovascular:
 Stroke
 Lower extremity gangrene
 Myocardial infarction
 Accelerated arteriosclerosis
 Diabetic nephropathy:
o Once a year
o + GFR
o All patients with t2DM
o T1DM with duration of 5 years
o All patients with comorbid hypertension
 Diabetic neuropathy
o All patients with diabetes
o At diagnosis of t2DM

12
 o 5 years after diagnosis of t1DM
o Types:
 Sensory:
 Polyradiculopathy
 Mononeuropathy
 Distant symmetric sensorimotor polyneuropathy
 Cranial mononeuropathy
 Auto-immune:
 Motor:
 Diabetic amyotrophy
 Diabetic retinopathy
o Exams every 1-2 years
 Foot care:
o At least annually
o Feet inspected at every visit
o Monofilament testing, pinprick, temperature, vibration
 Blood pressure measured at every visit
 Lipid profile at initiation of stantins, 4-12 weeks after 1 st dose and annually thereafter
 Diabetes prevention:
o 7% loss of initial body weight
o Moderate to intense physical activity 150min/week
o Metformin as prophylaxis for DM2 for >35 BMI, or >60 Yo
 Risk factors:
o T1DM
 Personal or family history of autoimmune disease
o T2DM
 First degree relative with DM
 Age >40
 Obesity (especially abdominal)
 Prior GDM, macrosomic baby >4 kg
 PCOS
 History of IGT or IFG
 Presence of complications associated with DM
 Presence of associated disease: PCOS, acanthosis nigricans,
psychiatric disorders, HIV
 Medications: glucocorticoids, atypical antipsychotics, HAART
Heart failure
Davidson

 Describes the clinical syndrome that develops when the heart cannot maintain adequate
output or can do so only at the expense of elevated ventricular filling present.
 Almost all forms of heart disease can lead to heart failure.
 Causes unplanned hospital visit.
 The most common etiology is coronary artery disease and myocardial infarction

13
 Approximately 50% of patients with severe heart failure due to left ventricular
dysfunction will die within 2 years, because of either pump failure or malignant
ventricular arrhythmias.
 HF may develop suddenly as in MI, or gradually, as in progressive valvular heart disease.
 Pathophysiology:
 Impaired systolic contraction, Impaired diastolic relaxation of both.
 Stimulation of the renin-angiotensin-aldosterone system leads to V.C., sodium and
water retention, and sympathetic activation. This is mediated by angiotensin II, a
potent constrictor of arterioles  prolonged sympathetic stimulation causes
negative effects, including cardiac myotic apoptosis, hypertrophy and focal
myocardial necrosis. Also causes peripheral vasoconstriction and arrhythmias.
Sodium and water retention is promoted by the release of aldosterone, endothelin-1
( a potent vasoconstrictor peptide with marked effects on the renal vasculature) and
in severe HF, ADH. Natriuretic peptides aren’t released from the atria in response to
atrial stretch, and act as physiological antagonists to the fluid-conserving effect of
aldosterone.
 After MI, cardiac contractility is impaired and neurohormonal activation causes
hypertrophy of non-infarcted segment, with thinning, dilatation and expansions of
the infarcted segment.
 Pulmonary and peripheral edema occurs because of high left and right atrial
pressures. This is compounded by sodium and water retention, caused by
impairment of renal perfusion and by 2ry hyperaldosteronism.
 Types of heart failure:
 Left-sided HF
 A reduction in LV output + increase in LA venous pressure + increase in
pulmonary venous pressure.
 an acute increase  pulmonary congestion or pulmonary edema
 a more gradual increase in left atrial pressure as that occurs in mitral stenosis 
reflux pulmonary vasoconstriction  protects the patient from pulmonary
edema  pulmonary hypertension  impair right ventricular function
 right-sided HF
 reduction in RV output and an increase in right atrial and systemic venous
pressure.
 Causes of isolated right HF include chronic lung disease (cor pulmonale),
pulmonary embolism and pulmonary valvular stenosis.
 Clinical assessment:
 Acute left HF:
 Presents with a sudden onset of dyspnea at rest that rapidly progresses to acute
respiratory distress, orthopnea and prostration (‫)زي السجود‬.
 The patient is agitated, pale and clammy (quality of being cold + dry). The
peripheries are cool to the touch and pulse is rapid.
 The BP is usually high because of sympathetic activation.
 The jugular venous pressure (JVP) us usually elevated.
 Auscultatory findings in pulmonary edema are crepitation at the lung bases, or
throughout the lungs if pulmonary edema is severe.
 Chronic HF:

14
  With periods of stability and episodes of decompensation, leading to worsening
symptoms that may necessitate hospitalization.
 Low cardiac output causes fatigue, listlessness and poor effort tolerance; the
peripheries are cold, and the BP is low. To maintain perfusion of vital organs,
blood flow is diverted away from skeletal muscle and this may contribute to
fatigue and weakness. Poor renal perfusion leads to oliguria and uremia.
 Pulmonary edema due to left HF presents with inspiratory crepitations over the
lung bases. In contrast, right HF produces a high JVP with hepatic congestion and
dependent peripheral edema. In ambulant patients, the edema affects the
ankles, whereas in bed-bound patients it collects around thighs and sacrum.
Ascites or pleural effusion may occur,
 It is associated with marked weight loss (cardiac cachexia), caused by
combination of anorexia and impaired absorption due to low cardiac output and
skeletal muscle atrophy due to immobility.
 Complications:
 Renal failure:
 By poor renal perfusion due to low cardiac output
 Exacerbated by diuretic therapy, angiotensin-converting enzyme inhibitors and
angiotensin receptor blockers.
 Hypokalemia:
 Result of treatment with potassium sparing diuretics or hyperaldosteronism
 Hyperkalemia
 Hyponatremia
 Impaired liver function
 By hepatic venous congestion and poor arterial perfusion which causes mild
jaundice and abnormal liver function tests; reduced synthesis of clotting factors.
 Thromboembolism
 Atrial and ventricular arrhythmias
 Investigation:
 Serum urea, creatinine and electrolytes, Hb, thyroid function, ECG and chest X-ray.
 Atrial fibrillation:
 Atrial fibrillation (AFib) is the most common heart rhythm abnormality, affecting more than
33 million people worldwide. Patients with AFib are at a higher risk of stroke if not
properly treated.
 Diagnosed by ECG
 Symptoms:
 Heart racing
 Fatigue
 5 times risk for stroke
 Adverse consequences are related to reduced blood flow from the heart and from clots
that may form in the heart

Headache syndrome
Davidson

15
 Tension-type headache: most common type. Pathophysiology: emotions and anxiety are
common precipitants + associated depressive illness. Clinical features: pain of tension
headache is characterized as dull, tight, or like pressure + sensation of a band around the
head. Often radiates forward from the occipital region. In contrast to migraine the pa9n
can remain unabated for weeks or months without interruption + no associated
vomiting or photopia. Pain may be less noticeable when patient is occupied. Tenderness
may be present over the skull. Analgesia have little effect.
 Migraine: before middle age. 20% of females and 6% of males affected at some point in
their lives. Pathophysiology: cause of migraine is unknown. Aura is due to dysfunction of
ion channels causing a spreading front of cortical depolarization (excitation) followed by
hyperpolarization (depression of activity). The headache phase is associated with
vasodilation of extracranial vessels relayed by hypothalamic activity. Activation of the
trigeminovascular system is probably important + family history. The female
predominance also suggests hormonal influences. Estrogen-containing contraception
sometimes exacerbates migraine. Migraine attack often occurs after a period of stress,
being more likely on the end of the week or at beginning of a holiday. Clinical features:
malaise, irritability, or behavioral change for some hours or days. 20% experience an
aura known also as classical migraine. The aura is most often visual, consisting of
fortification spectra, which are shimmering, salivary zigzag lines that march across the
visual fields for up to 40 minutes, sometimes leaving a trial of temporary visual field loss
(scotoma). In some sensory aura of tingling followed by numbness, spreading over 20-30
minutes, from one part of the body to another. Transient speech disturbance. 80% of
patients with characteristic headache but no aura also called common migraine. Usually
severe and throbbing with photophobia, phonophobia, and vomiting lasting 4-27 hours.
Movement makes the pain worse, patient prefer to lie in a quiet, dark room.
 Medication overuse headache: can complicate any other headache syndrome, but is
especially associated with migraine and tension headache.
 Cluster headache: also called migrainous neuralgia. Less common. 5:1 male
predominance. Onset is usually in the third decade. Pathophysiology: idiopathic. Differs
from migraine in its character, lack of genetic predisposition, lack of provoking dietary
factors. Abnormal hypothalamic activity. Patients more often are smokers and higher
than average alcohol consumption. Clinical features: periodic. Patients may experience
one or several attacks within a 24-hour period. It causes severe, unilateral periorbital
pain with autonomic features such as unilateral lacrimation, nasal congestion, and
conjunctival injection (occasionally with the other features of Horner’s syndrome). Pain
is characteristically brief (30-90 minutes). Patients are often highly agitated during the
headache phase. The cluster headache is typically a few weeks followed by remission for
months to years. But a small proportion do not experience remission.
 Trigeminal neuralgia: unilateral lancinating (tearing) facial pain, involving the 2nd and/or
3rd divisions of trigeminal > 50 years old. Pathophysiology: caused by irritative lesion
involving trigeminal root zone. Trigeminal neuralgia associated with multiple sclerosis
may result from a plaque of demyelination in the brain stem. Clinical features: pain is
repetitive, severe and very brief. Triggered by touch, a cold with or eating. Physical signs
absent, although the spasms may make the patient wince and sit silently.
 Headaches associated with specific activities: usually affect men in their thirties and
forties. Patient develop a sudden, severe headache with exertion, including sexual
activity. No vomiting and no neck stiffness, the headache lasts < 10-15 minutes.

16
Hypertension
Davidson

 Hypertension:
 Systemic BP rises with age
 Etiology:
 Hypertension is more common in some ethnic groups e.g. African americans and
Japanese and approximately 40-60% is explained by genetic factors.
 Environmental factors:
 High salt intake
 Heavy alcohol consumption
 Obesity
 Lack of exercise
 Impaired intrauterine growth
 Approach to newly diagnosed hypertension:
 A BP check is advisable every 5 years in adults.
 Measurements of blood pressure:
 Life-long treatment
 Measurements should be made to the nearest 2 mmHg, in the setting position
with the arm supported, and repeated after 5 minutes rest if the first recording is
high.
Hepatitis
Osmosis + Davidson
 Hepatitis is considered if transaminase is high
 Clinical features of acute infection
 Headache, myalgia, arthralgia, nausea, anorexia, dark urine, pale stool, jaundice.
 Liver is usually tinder, but minimally enlarged. Occasionally mild splenomegaly
 Symptoms rarely last > 3-6 weeks
 Complication may occur but rare.
 Viral hepatitis:
 Cytotoxic killing  cell apoptosis  liver damage
 Symptoms:
 Fever, malaise, and nausea.
 Hepatomegaly
 Inflamed liver
 Pain
 High blood transaminase (from leakage of apoptotic cells into blood) ALT>AST
 HAV:
 Highly infectious
 No history of jaundice
 Infection is more common in areas of overcrowding and poor sanitation
 Water, shellfish have been the route of transmission
 IgM is diagnostic of an acute infection

17
  Fecal oral transmission
 There is available vaccine
 Occurs in travelers
 Acute only
 No role for anti-viral medications
 HEV:
 Fecal oral
 Endemic in India, middle east
 Undercooked sea-food
 Acute only, no chronic state
 Infection to pregnant women is severe  acute liver failure
 HCV:
 Children
 Acute symptomatic infection is rare
 Most are unaware of when they became infected
 80% become clinically infected
 Most individual remain asymptomatic until progression to cirrhosis
 Fatigue can complicate chronic infection
 Investigation:
 may take 6-12 weeks for Ab to appear in blood following acute infection such
as needlestick injury.
 LFT between 50-200 u/L, jaundice is rare, only usually appear in end stage
cirrhosis.
 Liver biopsy, using netavir system, which scores fibrosis from 1-4. 4
cirrhosis.
 Sexual transmission
 Acute + chronic
 HCV RNA test
 HBV:
 The virus also called Dane’s particles and an excess of its surface protein circulate
in blood
 Humans are only source of infection
 Most common cause of chronic liver disease
 Most common cause of hepatocellular carcinoma
 May cause acute viral hepatitis  often asymptomatic. Particularly when
acquired at birth, many with chronic hepatitis B often asymptomatic too.
 Vertical transmission is most common cause of infection, highest risk of ongoing
chronic infection.
 Chronic hepatitis  cirrhosis, HCC after decades of infection.
 Virus is not directly cytotoxic, rather it is immune response to viral Ag.
 Investigation:
 HBsAg
 Indicator of active infection, -ve test HBV very unlikely.
 > 6 months  chronic infection
 IgM can sometimes reveal an acute HBV infection when HBsAg has
disappeared and before anti-HBs has developed
 HBeAg  active replication of virus in liver

18
  HBsAg, anti-HBc (IgG)  chronic infection
 Low HBeAg  low viral replication
 Acute + chronic
 HBV surface Ag
 HDV:
 No independent existence
 Transmission is by close contact, vertical transmission
 Effective management of HBV prevents HDV infection.
 Needs HBV to cause disease
 IgG or IgM  active infection
 Auto-immune hepatitis
 Female: male 4:1
 MHC-II  HLA-DR3, HLA-DR4
 Associated with other autoimmune disease
 Type 1:
 80%
 High PTT
 Low albumin
 Type 2:
 Less common
 Ab to ALKM-1
 Ab to ALC-1
 Young girls
Infective endocarditis
Danish

 Microbial infection of a heart valves or lining of a cardiac chamber.

 Predisposing factors:
 Rheumatic heart diseases
 Mitral regurgitation
 Mitral stenosis
 Aortic stenosis
 Aortic regurgitation
 Congenetal heart diseases
 Bicuspid aortic valve
 Mitral valve prolapse
 Calcified aortic valve disease
 Prosthetic valves
 Streptococcus viridians
 They may enter the blood stream on chewing, teeth brushing, or dental
extraction
 enterococcus faecalis
 more common in older men with prostatic disease
 more common in women with genitourinary infection
 streptococcus aureus
 common cause of infective endocarditis
19
  originate from skin infections, abscesses or IV drug abuse
 post-operative endocarditis follows cardiac surgery and affects native or prosthetic
valve.
 Organism is staph. Albus
 Gram negative bacilli
 Associated with prosthetic valves.
 Fungal infection (candida, aspergillus)
 Affects drug addicts and immunosuppressed patients.
 Non-bacterial thrombotic endocarditis:
 Noninfective causes of endocarditis are
 Old age
 Malignancy
 Disseminated intravascular coagulation
 Uremia
 Burns
 SLE
 Pathology
 More common on the left side producing mitral and aortic regurgitation. Right sided
valves are involved in IV drug abusers
 Endothelial damage by infection leads to deposition of platelets and fibrin, colonized
by blood borne organism. This mass that is composed of fibrin, platelets and
infecting organisms is known as vegetation  may become large enough to cause
obstruction or break away as emboli
 Local destructive effects of intracardiac infection:
 Destruction of valve cusp
 Rupture of chordae tendinae
 Paravalvular abscess
 Large vegetations  functional valvular stenosis
 Types:
 Subacute endocarditis
 Acute
 Prosthetic
 Subacute endocarditis:
 Organism of relatively low virulence
 Commonest organism is strep. Viridans
 Suspected when a patient known to have congenital or valvular heart disease
develop a persistent fever, unusual tiredness, night sweats, weight loss.
 Acute endocarditis:
 Highly virulent and invasive organism e.g. staphylococcus aureus.
 Can affect damaged valves but can also occur in hearts with no previous defects e.g.
intravenous drug abuse.
 Present with severe febrile illness with prominent and changing heart murmur
 Prosthetic endocarditis:
 Following cardiac surgery in which prosthetic heart valves are used.
 Organism is staphylococcus epidermidis, staph. Aureus
 Produces myocardial abscess and damage to conduction system.
 Clinical features

20
  Features of bacteremia:
 Fever
 Fever that has lasted several days to 2 weeks
 May be absent in older individuals
 Petechiae
 They are small, and red, usually with pale center in mucosa of pharynx and
conjunctiva
 Splenomegaly
 30-40% of cases in long standing endocarditis
 Features of immune complexes
 Janeway lesions:
 Small, flat, erythematous, non-tender macules on thenar and hypothenar
eminence.
 Splinter hemorrhage
 Under finger or toe nails
 Osler’s nodes
 Hard, painful, tender subcutaneous swellings occurring at fingertips.
 Features of valvular dysfunction
 Murmur
 Abnormal heart sound
 Regurgitation
 Features of embolism
 Infarctions
 Brain (stroke)
 Kidney (hematuria)
 Heart (MI)
 Intestine (intestinal infarction)
 Spleen (splenic infarction)
 Extremities (gangrene)
 Right sided endocarditis (pulmonary embolism)
 Examination of patient with endocarditis
 Hands
 Clubbing, splinter hemorrhage, Osler’s nodes and janeway lesions.
 Eyes
 Roth’s spots (oval shaped lesion with clear spot in the middle) in fundus,
conjunctival petechiae.
 precordium
 Murmur
 Lungs
 Crepitation due to failure
 Abdomen
 Splenomegaly
 Lower limb
 Weakness of paralysis
 Urine analysis
 Hematuria and proteinuria
 Investigation

21
  Blood culture
 Three sets of blood culture from different venipuncture sites over 24 hours
before starting antibiotics
 Positive in 95% of cases
 Causes of negative culture
 Antibiotic therapy before obtaining culture
 Fungal infection
 Organisms that require special media  legionella
 Slow growing organisms  Brucella, anaerobes
 Other blood tests
 Anemia
 C-reactive protein and ESR are raised
 WBC count is elevated in acute endocarditis while usually normal in subacute
endocarditis
 Thrombocytopenia may be present but rare.
 ECG
 Chest X-ray
 Urine analysis
 Diagnosis of endocarditis
 When patient with fever presents with one or more of the cardinal elements
 Predisposing cardiac lesion
 Bacteremia
 Embolic phenomenon
 Active endocardial process
 Modified duke’s criteria for the diagnosis of endocarditis
 Major criteria
 Positive blood culture
 for microorganism that typically causes infective endocarditis
 Persistent positive culture
 From two separate blood cultures drawn more than 12 hours apart
 Positive endochardiography
 Definite vegetation or myocardial abscess or new partial dehiscence of
prosthetic valve
 Development of new murmur of regurgitation
 Minor criteria
 Predisposing factors
 Fever > 38 C
 Vascular phenomena
 Major arterial emboli
 Janeway lesion
 Conjunctival hemorrhage
 Mycotic aneurysm
 Immunologic phenomenon
 Glomerulonephritis, Osler’s nodes, Roth’s spots
 Microbiological evidence
 Positive blood culture but not meeting the major criteria

22
  Echocardiogram consistent with infective endocarditis but not meeting major
criteria
 Complications
 Congestive heart failure
 Valvular damage  valvular regurgitation
 Valvular stenosis
 Systemic embolism
 Mycotic aneurism

Peptic ulcer
Davidson

 Peptic ulcer can occur in lower esophagus, stomach or duodenum and rarely in ilium
adjacent to mackle’s diverticulum.
 Acute ulcers  no evidence of fibrosis, erosions do not protrude mscularis mucosa.
 Gastric and duodenal ulcer: male: female = 5:1 or 2:1. Chronic GASTRIC ulcer isusually
single. 90% in lesser curvature. Chronic DUODENAL ulcer usually in 1 st part, 50% are on
anterior wall.
 H. pylori: 50% > 50 YO are affected. Vast majority of colonized people remain healthy
and asymptomatic only a minority develop the disease. 90% of DUODENAL ulcer, 70% of
GASTRIC ulcer patients are infected with H. pylori, remaining 30% by NSAID. The bacteria
produces ammonia from urea + raises pH around bacterium, cell wall membrane layer
 chronic gastritis. In most people H. pylori causes localized antral gastritis associated
with depletion of somatostatin + increased Gastrin  hypergastrinemia  high acid by
parietal cells. In 1% of infected people H. pylori causes pangastritis. Leading to gastric
atrophy + hypochlorhydria  allows other bacteria to proliferate within stomach 
producing mutagenic nitrites from nitrates  predisposing to gastric carcinoma. CagA
 interact with numerous cell signaling pathways involved in cell replication and
apoptosis + IL-8  inflammation. VacA  causes increased cell permeability, efflux of
macronutrient from epithelium, induction of apoptosis + suppression of local immune
cell activity.
 Smoking: increase risk for gastric ulcer. Make ulcer less likely to heal, more likely for
complication
 Clinical features: with spontaneous relapses and remission for decades. Recurrent
abdominal pain, localized to epigastrium, relationship to food, occasional vomiting in
40%.
 Investigation: endoscopy is preferred  must always be biopsied and followed up. Urea
breath test (tagged CO2 indicate H. pylori infection), fecal Ag are best because of
accuracy + non-invasive.
 Complication of peptic ulcer: shoulder tip pain is caused by irritation of diaphragm 
irritating phrenic nerve  referred pain to shoulders. Accompanied by shallow
respiration due to limitation of diaphragmatic movements. Perforation carries a
mortality of 25% due to peritonitis.
 Gastric outlet obstruction: nausea, vomiting, and abdominal pain. Show evidence of
wasting, dehydration. Visible gastric peristalsis is diagnostic. In some patients, PPI drugs
e=heal ulcers, relieve pyloric edema and overcome need for surgery.
23
 Zollinger-Ellison syndrome: triad of severe peptic ulceration + gastric acid hypersecretion
+ gastrinoma. Most common between 30-50 years of age. Diarrhea + steatorrhea. 90%
of tumors occur in pancreatic head of proximal duodenal wall. Severe _ multiple peptic
ulcers in unusual sites. In 30% of patients present with diarrhea. Injection of hormone
secretin  paradoxical and dramatic increase in gastrin.
 GASTRIC ulcer pain increase with eating  weight loss.
 DUODENAL ulcer  weight gain.

Pleural effusion
Davidson

 Accumulation of serous fluid within the pleural space. Accumulation of frank pus is
termed empyema, that of blood is hemothorax, and that of chyle  chylothorax. A
pleural fluid accumulates as a result of either increased HP or decreased
OP(transudative effusion, as seen in cardiac, liver or renal failure. Or from increased
microvascular pressure.
 Clinical assessment: symptoms  pain on inspiration and coughing.
 Signs: 1. inspection  tachypnea. 2. Palpation  low expansion + trachea and apex
may be moved to other side. 3. Percussion  stony dull. 4. Auscultation  absent
breath sounds and absent vocal resonance + bronchial breathing or crackles heard
above effusion.
 Investigation: chest film is of curved shadow at the lung base, blunting the costophrenic
angle. Fluid track up the lateral chest wall. Around 200mL of fluid is required in order for
it to be detectible of PA chest X-ray. US is more accurate for determining the presence of
fluid. Presence of sepetation suggests an evolving empyema or resolving hemothorax.
 Pleural aspiration and biopsy: simple aspiration provides info on the color and texture of
fluid and these alone may immediately suggest an empyema or chylothorax. The
presence of blood is consistent with pulmonary infarction or malignancy but may result
from a traumatic tap. A low pH suggest infection but may also be seen in rheumatoid
arthritis, ruptured esophagus or advanced malignancy.
 Empyema: this is a collection of pus in the pleural space. Microscopically, neutrophil
leukocytes are present in large numbers. It is usually Unilateral. It is always 2ry to
infection of nearby organ such as the lung, most commonly due to the bacterial
pneumonias and TB. Over 40% of patients with CAP develop as associate pleural effusion
(Para-pneumonic effusion). Other causes are infection of a hemothorax following
trauma or surgery, esophageal rupture and rupture of a sub-phrenic abscess through the
diaphragm. CLINICAL ASSESSMENT: should be suspected in patients with pulmonary
infection if there is severe pleuritic chest pain or persisting or recurrent pyrexia, despite
appropriate antibiotic treatment. Once empyema has developed, systemic features are
prominent. INVESTIGATION: chest X-ray appearance may be indistinguishable from
pleural effusion but can form a D- shaped shadow. US or CT is used to identify the
optimal site for aspiration using a wide bore needle. Other features suggesting
empyema  1. fluid glucose < 3.3mmol/L (60mg/dL). 2. LDH > 1000 U/L. 3. pH < 7.0. pus
measurements should be avoided if pus is thick.
Pneumonia
24
Davidson + osmosis

 An acute respiratory illness with pulmonary shadowing which may be segmental, lobar,
or multilobar.
 Pneumonia usually is classified as community or hospital acquired.
 Lobar pneumonia: homogenous consolidation of one or more lung lobes, often with
associated pleural inflammation. Inflammatory response in lobar pneumonia evolves
through stages of congestion, red then grey hepatization, and finally resolution. Stage1:
days 1-2 congestion  filled with fluid. Stage2: days 3-4  red hepatization (fibrin forms
 firm+ red like liver). Stage3: days 5-7  grey hepatization (still firm). Stage 4: day 8 –
3 weeks  resolution -
 Bronchopneumonia: patchy alveolar consolidation often affecting lower lobes.
 Community acquired pneumonia: 5-11/1000 affected each year. Particularly common at
extremes of age. Spread by droplet infection. Staph. Pneumoniae remains the most
common infecting agent. Mycoplasma pneumonia is more common in young people.
Whereas H. Influenza is more common in elderly. Legionella pneumophilia occurs in
local outbreaks centered on contaminated cooling towers. Pneumonia particularly lobar
pneumonia presents as an acute illness. Systemic features are fever rigors, shivering,
malaise, and delirium. Appetite lost and headache frequently reported. Cough at first
short and painful and dry  later mucopurulent sputum. Rust-colored sputum seen in
patients with strep. Pneumoniae and may report hemoptysis. Pain is referred to the
shoulder or anterior abdominal wall. On examination respiratory and pulse rate may be
raised and blood pressure low. Oxygen saturation on air may be low and patient
cyanosed and distressed. When consolidated, the lung is typically dull to percussion.
Auscultation reveals bronchial breathing and whispering pectoriloquy; crackles are
heard throughout. The presence of poral hygiene should prompt consideration of
klebsiellosis or actinomyces israelii. Prevention  current smokers should be advised to
stop; influenza and pneumococcal vaccination should be considered.
 Factors predisposing to pneumonia: cigarette smoking, URTI, alcohol, corticosteroid
therapy, old age, recent influenza infection, pre-existing lung disease, indoor air
pollution.
 Differential diagnosis for pneumonia: pulmonary infarction, TB, Pulmonary edema,
pulmonary eosinophilia, bronchoalveolar cell carcinoma.
 Hospital acquired pneumonia: occurring at least 2 days after admission to hospital,
elderly is particularly at risk, along with ICU, mechanically ventilated. Diagnosis for those
who develop purulent sputum, new radiological infiltrates, unexplained increase in
oxygen requirement, a core temperature > 38.5C. in contrast to CAP, microbial
confirmation should be sought whenever possible + CBC + urea and electrolytes _ ESR +
C-reactive protein and a chest X-ray performed. Prevention  risk of aspiration should
be minimized.
 Suppurative pneumonia, aspiration pneumonia and pulmonary abscess: characterized
by destruction of lung parenchyma by inflammatory process. Pulmonary abscess is
usually taken to refer to lesion in which there is large localized collection of pus, or a
cavity lined by chronic inflammatory tissue from which pus has escaped by rupture into
a bronchus. Additional risk factor for aspiration pneumonia include bulbar or vocal cord
palsy, stroke, achalasia, or esophageal reflux and alcoholism. Aspiration tends to localize

25
 to dependent areas of lung, such as apical segment of lower lobe in supine patient. May
also complicate local bronchial obstruction from a neoplasm or foreign body.
 Lamierre’s syndrome: cause of pulmonary abscesses agent is anaerobe F. necrophorum.
Sore throat, painful swollen neck, fever, rigor, hemoptysis, dyspnea, spread into jugular
veins leads to thrombosis and metastatic spread of organisms.
Presenting problems in thyroid disease

 Non-specific complains: tiredness and weight gain

 Thyrotoxicosis
 Elevated thyroid hormone in the blood
 Most common  Grave’s disease, Multinodular goiter, Toxic adenoma
 Clinical assessment:
 Weight loss, normal or increased appetite, heat intolerance, palpitations, tremor,
irritability, tachycardia, palmar erythema, lid lag
 Not all patients have palpable goiter
 All causes of thyrotoxicosis can cause lid retraction
 Only Grave’s disease cause periorbital edema, conjunctival irritation,
exophthalmos, diplopia, finger clubbing
 Thyroid storm:
 Fever, agitation, confusion, tachycardia, atrial fibrillation, HF in old
 10% mortality
 Hypothyroidism:
 I33 or surgery account for 90% of cases
 Women > men 6:1
 Low pitched voice, poor hearing, slurred speech, large tongue, compression of
median nerve (carpal tunnel syndrome) + myxedema
 Facial pallor  become anemic
 Taking extra levothyroxine  inhibit TSH  risk factor (osteoporosis, atrial
fibrillation)
 Measure thyroid function yearly
 Levothyroxine absorption is maximal at night and with vitamin C
 Myxedema coma:
 Body temperature almost 25
 High CSF pressure
 Hight CSF protein
 Usually in elderly
 Mortality 50%
 Thyroid lump or swelling:
 Women>men
 Majority are impalpable
 Only 5-10% of thyroid nodule are malignant
 Swelling moves on swallowing
 Grave’s disease
 igG Ab  TSH  stimulate thyroid hormone + proliferation of follicular cells 
goiter
 affects women 30-50 YO

26
  there may be reduction of visual acuity or visual consequences of corneal edema or
optic nerve compression
 periorbital myxedema in 10% pink purplish plaque on dorsum of foot.
 Hashimoto’s thyroiditis:
 Destructive lymphoid infiltration of thyroid  fibrosis, enlargement
 High risk of thyroid lymphoma
 Many presents with goiter
 Thyroid adenoma:
 High thyroid hormone  inhibit TSH
 Atrophy of rest of gland
 Papillary carcinoma:
 Irradiation induced cancer
 90% spread to LN
 Follicular carcinoma:
 Metastasizes to blood, bone, lungs and brain
 Medullary carcinoma:
 From parafollicular c-cells  calcitonin + serotonin
 Hypo-calcemic extremely rare
 Total thyroidectomy
Pulmonary embolism

 General characteristics:
 Sources of emboli
 Lower extremity DVT – PE is major complication of DVT
 Risk factors:
 Age >60 years
 Malignancy
 Prior history of DVT, PE
 Hereditary hypercoagulable state
 Prolonged immobilization or bed rest, long standing travel
 Cardiac disease, especially CHF
 Obesity
 Nephrotic syndrome
 Major surgery
 Major trauma
 Pregnancy, estrogen use
 Pathophysiology:
 Emboli block a portion of pulmonary vasculature  increased pulmonary
vascular resistance, pulmonary artery pressure, and right ventricular pressure. If
it is severe (large blockage), acute cor pulmonale may result.
 Dead space is created in areas of the lung in which there is ventilation but no
perfusion. The resulting hypoxemia and hypercarbia drive respiratory effort 
tachypnea
 Course and prognosis:
 Most often, PE is clinically silent. Recurrences are common  development of
chronic pulmonary HTM. And chronic cor pulmonale

27
  When PE is undiagnosed, mortality approaches 30%.
 Clinical features:
 Symptoms
 Dyspnea 73%
 Pleuritic chest pain 66%
 Cough 37%
 Hemoptysis 13%
 Only one third of patients with PE will have signs and symptoms of DVT
 Syncope is seen in large PE
 Signs
 Tachypnea 70%
 Crackles 51%
 Tachycardia
 S4
 Increased P2
Renal failure
Danish

 Etiology:
 May be due to pre-renal, renal o post-renal
 Pre-renal ARF (pre-renal azotemia):
 Kidneys inadequately perfused (hypoperfusion) and GFR greatly diminished due
to:
 GI loss
 Vomiting
 Diarrhea
 Renal loss:
 Diuresis
 Skin loss
 sweating
 Low cardiac output e.g. cardiac failure.
 Under-filling of vascular bed due to hemorrhage due to trauma, GI bleeding,
surgery, complications of pregnancy.
 Renal artery stenosis
 Hepatorenal disease
 Na+ < 10-20
 Severe fluid depletion or vasodilation resulting from sepsis.
 Sodium and water depletion:
 Acute intestinal obstruction
 Severe vomiting
 Diarrhea
 Pancreatitis
 Fistula
 Cardiovascular shock
 Renal:

28
  Vasculitis or microangiopathic hemolytic states, rapidly progressive (crescentric)
glomerulonephritis.
 Injury to tubular cells (acute tubular necrosis) by toxins or ischemia.
 Acute intestinal nephritis due to infections or drug reaction.
 Post-renal:
 Benign prostatic hyperplasia
 Cancer of ureter or urethra
 ARF is caused by obstruction of the urinary tract at any point in its course.
 Pre-renal:
 Clinical features:
 Hypotension and signs of inadequate peripheral perfusion
 Decreased urinary output
 Diagnosis:
 A progressive increase in blood urea and plasma creatinine
 Serum BUN: creatinine ratio > 20/1
 Intrinsic renal disease:
 May result from:
 Acute tubular necrosis (tubular):
 Most common cause of renal failure. Tubular cells have the capacity to
regenerate and therefore returns to near normal if patient can be kept alive
during regeneration phase
 Types:
 Ischemic type:
 By prolonged ischemia due to hypoperfusion
 Nephrotoxic:
 Drugs (interstitial):
 Aminoglycosides, heavy metals (mercury)
 Endogenous toxins
 Calcium, uric acids, hemoglobinuria, myoglobinuria, uric acid
(gout).
 Exogenous toxins
 Antibiotics.
 Contrast dye.
 Primary glomerulonephritis (glomerular):
 Secondary glomerulonephritis (glomerular):
 Diabetic nephropathy
 Amyloidosis
 Systemic vasculitis: SLE, polyarteritis, Wegener’s granulomatosis.
 Clinical course:
 Relatively short 10-25 days
 Phases:
 Pre-oliguric phase (0-2 days)
 Oliguric phase (8-14 days)
 Diuretic phase (about 10 days)
 Recovery phase (4-6 months)
 Pre-oliguric phase:
 Period from occurrence of precipitating event until beginning of oliguria.

29
  Ratio of urea in urine to that in plasma becomes low 14:1
 Oliguric phase:
 Urine volume < 400 ml in 24 hours.
 The longer tha patient remains in this phase the poorer the prognosis due to
development of complications due to excessive body fluids, electrolyte
imbalance and retention of metabolic waste products.
 Diuretic phase:
 Characterized by increase in urinary output to about 3-5 liters daily and this
may progress to polyuria and dehydration.
 Diuresis develops because damaged tubular epithelium is replaced by an
epithelium which has nit yet developed concentrating activity.
 Recovery phase:
 Stabilization of serum laboratory values until patient attains either totally
normal or optimal renal function.
 Distinction from ARF due to renal and post renal cause:
 Urine analysis: hematuria with red-cell casts, recent trauma or sepsis with
hypotension and exposure to nephrotoxic drugs all suggest intrinsic disease
 Previous history of stone disease suggests obstructive nephropathy. Anuria
should always be considered due to obstruction until proven otherwise.
 Post-renal cause:
 Complications of ARF:
 Fluid overload
 Nausea, headache, lethargy, elevated JVP, ascites and pleural and pericardiac
effusion.
 Hyponatremia
 Hyperkalemia
 From impaired secretion of potassium which comes from the diet, potassium
containing fluids and potassium released from injured tubular cells.
 May lead to ventricular fibrillation
 ECG changes of hyperkalemia: tall T-wave, flat P wave, increased PR interval
widening of QSR complex.
 Infections
 Metabolic acidosis
 Malnutrition
 Anemia
 Bleeding disorders
 Cardiac arrhythmias
 GIT bleeding
 Uremic syndrome
 Interstitial nephritis:
 Etiology:
 Drugs:
 Peicillins, cephalosporins, sulphanomides, rifampicin, phenytoin, NSAIDs,
allopurinol, frusemide.
 Systemic disease:
 SLE
 Sarcoidosis

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  Sjogren’s syndrome
 Multiple myeloma
 Cryoglobinemia
 Infections
 Leptospirosis
 Streptococcal infection
 Tuberculosis
 Pyelonephritis
 Cytomegalovirus
 Clinical features:
 Fever, rash, arthralgia, acute renal failure.
 Papillary necrosis:
 Infection of renal pyramids that is associated with vascular disease of kidney or
urinary tract obstruction. It is usually bilateral.
 Predisposing factors:
 Diabetes
 SCA
 Chronic alcoholism
 Chronic urinary tract obstruction
 Clinical features:
 Fever, chills
 Hematuria
 Pain in flank or abdomen due to obstruction of ureter by necrotis tissue
 ARF with oliguria and anuria
 Asymptomatic sloughing of pyramid with chronic urinary infection detected
when necrotic tissue is passed in urine.
 Diagnosis
 Necrotic tissue in urine
 Ring shadow on IVP representing radiolucent sloughed papilla surrounded by
radiodense contrast material in calyx.
 Drug-induced impairment of renal function:
 Pre-renal:
 Hypovolemia: due to:
 Frusemide esp. in elderly patients
 Hypercalcemia causing renal salt and water loss.
 Decreased cardiac output which impairs renal perfusion. E.g. due to B-blockers
 Decreased renal blood flow e.g. due to ACE inhibitors
 Renal:
 By direct nephrotoxicity:
 Aminoglycosides
 Amphotericin B
 Cephaloridine
 Heavy metals
 Carbon tetrachloride
 Cell mediated nephritis:
 Sulphanomides
 NSAIDs

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  Penicillins
 Chronic tubulointerstitial nephritis
 Immune complex mediated glomerulonephritis produced by penicillamine.
 Post-renal
 Retroperitoneal fibrosis with urinary tract obstruction may result from
methylsergide.
 Minimal change disease (nil disease):
 Type of nephrotic syndrome:
 The glomeruli are damage so allow plasma proteins to pass into the urine leading
to proteinuria > 3.5 g/day  hypoalbuminemia  low OP  low osmotic
pressure  water driven out into tissues  edema.
 Increased lipid in blood  lipiduria.
 T-cells in blood release cytokines that damages the podocytes  making them
flat out (effacement) so albumin is filtered out with the urine. Although not
allowing immunoglobulin is not filtered  selective proteinuria
 In most cases is idiopathic but may be associated with Hodgkin’s lymphoma.
 Diagnosis:
 EM:
 Effacement of foot processes of podocytes.
 Treatment:
 Corticosteroids.
 Goodpasture syndrome:
 Is an autoimmune disease that primarily affect the kidneys and lung
 Kidney:
 Hematuria
 Proteinuria
 Lungs:
 restrictive lung disease
 Inflammation and bleeding (hemoptysis)
 Most abundant collagen in basement membrane of kidneys and the alveoli in the
lung is collagen IV
 Autoantibody bind to alpha 3 chain
 Type II hypersensitivity reaction
 Activate complement system  release enzymes (peroxidase, myeloperoxidase,
proteinase-3)  free oxygen radicals  damage basement membrane,
endothelium, organ itself.
 Risk factors:
 Genes that code for HLA-DRI5
 Environmental
 Infection
 Smoking
 Oxidative stress
 Hydrocarbon-based solvents (people in dry cleaning industry)
 Lung symptoms usually precede kidney symptoms  restrictive lung disease
 Diagnosis:
 Biopsy of the kidney:
 Inflammation of basemen membrane

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  Treatment:
 Corticosteroids
 IgA nephropathy:
 Benign in 60% but symptomatic in 40%
 Most common cause of nephropathy
 Type of nephritic syndrome

Rheumatology and bone diseases
Danish

 Rheumatic arthritis:
 Is a chronic symmetrical polyarthritis of unknown cause, characterized by chronic
inflammatory synovitis of mainly peripheral joints, with extra-articular features.
 Progressive joint damage causing severe disability.
 Female: male 3:1.
 Risk factors:
 Genetic factor usually associated with HLA-DR4, DR1
 Autoimmune because autoantibodies are present + immune complexes are
common in synovial-fluid and circulation
 Female gender
 Cigarette smoking
 Pathogenesis:
 There is swelling and congestion of synovial membrane and underlying
connective tissue which becomes infiltrated with lymphocytes, plasma cells and
macrophages
 Clinical features:
 Insidious onset of pain and stiffness in the small joints of hands and feet. In 25%
of cases it presents as monoarthritic such as involvement of only knee joint
 Typical presentation of RA:
 Classic (chronic persistent): 70%
 Fatigue, generalized weakness and vague musculoskeletal symptoms for
weeks or months and then pain, stiffness and swelling of small joints of hands
and wrist
 It may be seropositive or negative for rheumatic factor
 Seropositive patients develop more joint damage as compared to
seronegative.
 Acute: 15%
 Often accompanied by constitutional symptoms e.g. fever, lymphadenopathy
and splenomegaly.
 Palindromic: 5%
 Stiffness usually of single joint lasting only a few hours or days followed by
rapid return to normal
 Transient:
 Self-limiting disease lasting less than 12 months and leaving no permanent
joint damage

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  It is usually seronegative for IgM rheumatoid factor
 Remitting:
 There is a period of several years during which the arthritis is active but
remits, leaving minimal damage
 Symptoms:
 Joint pain
 Worst on waking in the morning and improves progressively with activity
 There is often pain at night disturbing the sleep
 Morning stiffness
 For several hours then subsides
 General symptoms
 Fatigue and malaise
 Extra-articular symptoms
 Symptoms:
 Swelling (by effusion or synovial proliferation).
 Warmth
 Tenderness
 Limitation of movement (with muscle wasting around affected joints)
 Deformities (at later stages)
 Subcutaneous nodules
 Pattern of joint involvement: (most affected)
 Proximal interphalangeal and metacarpophalangeal joints of fingers
 Wrist
 Knee
 Ankle
 Toes
 D/D from osteoarthritis:
 In osteoarthritis, number of joints affected is much less than RA
 Joints most commonly affected in OA are weight bearing joints e.g. knee and hip
joints
 Deformities:
 Spindling of fingers
 Swan neck deformity
 Hyperextension at proximal interphalangeal joints and fixed flexion at distal
interphalangeal joints.
 Button hole deformity
 Fixed flexion of proximal interphalangeal joint and extension of distal
interphalangeal joint.
 Z deformity of the thumb
 Loss of thumb mobility
 Carpal tunnel syndrome
 Tenosynovitis at the wrist can entrap the median nerve.
 Extra – articular features
 Palmar erythema
 Vasculitis lesions in nail beds, nail folds and digital pulp

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  Lateral deviation of the toes and subluxation (partly dislocation) of the
metatarsophalangeal joints so that head of metatarsals becomes palpable in the
soles of the feet and patient often describes as sensation of walking on stones
 Ankle develops valgus deformity
 Synovial effusion in the knee causes quadriceps wasting
 Baker’s cyst:
 Extension of inflamed synovium into popliteal space, causing pain and
swelling.
 High pressure generated by flexion of knee can cause rupture of cyst into the
calf manifesting as calf swelling, tenderness and pitting edema
 Complication of RA:
 Ruptured tendons
 Ruptured Baker’s cyst
 Joint infection
 Spinal cord compression
 Amyloidosis presenting as nephrotic syndrome
 Osteoarthritis
 Is also called degenerative bone disease is the end result if variety of patterns of joint
failure
 Characterized by degeneration of articular cartilage and simultaneous proliferation
of new bone, cartilage and connective tissue.
 Its greatest impact is on weight bearing joints e.g. hip and knees
 No extra – articular features and no systemic illness
 Etiology
 Primary  unknown
 2ry  response to a recognizable local or systemic factor
 Pathogenesis
 Mechanical insults  trauma
 Biochemical abnormalities of cartilage
 Chondrocytes in cartilage are believed to initiate the deterioration by relasing
enzymes that degrade collagen and proteoglycan  break in the collagen
fibers which allows the uptake of water as a result cartilage swells and splits
 Pathology
 Thickening of subchondral bone with cyst formation
 Pattern of joint involvement
 Nodal
 Middle aged woman
 Bony swelling of distal interphalangeal join  Heberden’s nodes
 Swelling of proximal interphalangeal joint  Bouchard’s nodes
 Non-nodal
 Erosive
 Severe osteoarthritis
 Episodic signs and symptoms of joint inflammation with development of
destructive subchondral erosions in proximal and distal interphalangeal joints
 Osteoarthritis of knees
 Associated with obesity
 More common in women

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  Symptoms
 Pain
 In knees, hip, hands
 Worst In evening
 Aggravated by use and relived by rest
 Intermittent at first but later chronic
 Morning stiffness
 Up to half an hour
 Disability
 Movement becomes increasingly limited, initially as a result of pain and
muscular spasm but later because of capsular fibrosis, osteophyte formation
and remodeling of bones
 Signs
 Joint swelling
 Characteristically hard and bony sometimes with associated effusion
 Crepitus
 On movement may be felt or even heard
 Muscle wasting of muscle around joints
 Joint deformities
 Particularly in knee joint, valgus (outward) or Varus (inward) or flexion
deformity
 Hands
 Heberden’s node
 Bony swelling of distal interphalangeal joint of fingers and Bouchard’s nodes
at proximal interphalangeal joints
 At 1st the joints are often red, warm, swollen and very tender later
inflammation disappear leaving knobby but often painless swelling
 Feet
 Metatarsophalangeal joint is often affected called “poor man’s gout”
 Investigation
 X-ray
 Narrowing of joint space due to loss of cartilage
 Formation of osteophytes at the margin of joints
 Sclerosis of underlying bone
 Cyst formation
 Blood count, ESR are normal
 Synovial fluid is viscous and has low cell count
 Infective arthritis
 Septic arthritis (non-gonococcal acute bacterial arthritis):
 Is an acute onset bacterial inflammation usually involving single joint in > 90%.
Most often in knee joint and wrists, in IV drug abusers infection of spine and
sacroiliac joints is more common
 Etiology
 Most common organism is Staph. Aureus, streptococci and gram-negative
bacilli such as E. coli and pseudomonas
SCA + thalassemia
36
Davidson

 Sickle-cell anemia
 Single glutamic acid to valine substitution at position 6 of beta globin polypeptide
chain. It is inherited as an AR trait. Homozygotes only produce abnormal beta chain
that make hemoglobin S. heterozygotes produce a mixture of normal and abnormal
beta chains that make normal HbA and HbS.
 Epidemiology:
 Individuals with sickle-cell trait are relatively resistant to the lethal effects of
Falciparum Malaria in early childhood.
 Homozygous patients with SCA do not have correspondingly greater resistance to
Falciparum Malaria.
 Pathogenesis:
 When Hemoglobin S is deoxygenated, the molecules of hemoglobin polymerase
to form pseudocrysralline structures known as tactoids. These distort the red cell
membrane and produce characteristic sickle-shaped cell.
 Clinical features:
 Sickling is precipitated by hypoxia, acidosis, dehydration and infection.
Irreversibly sickled cells have a shortened survival and plug vessels in the
microcirculation
 Crisis:
 Painful VASO-OCCLUSIVE crisis:
 Plugging of small vessels in the bone produces acute severe bone pain.
This affects areas of active marrow: the hands and feet in children
( dactylitis) or femora, humeral, ribs pelvis and vertebra in adults.
 Patients have systemic response with tachycardia, sweating and fever
 This is the most common crisis.
 SICKLE CHEST syndrome:
 Follow a vasoocclusive crisis and is the most common cause of death in
adult sickle disease.
 Bone marrow infarction results in fat emboli to the lungs, which cause
further sickling and infarction, leading to ventilatory failure if not treated.
 SEQUESTRATION crisis:
 Thrombosis of the venous outflow from an organ causes loss of function
and acute painful enlargement.
 In children, the spleen is the most common site.
 Massive splenic enlargement may result in severe anemia, circulatory
collapse and death.
 Recurrent sickling in the spleen in childhood results in infarction and
adults may have no functional spleen
 In adults, the liver may undergo sequestration with severe pain due to
capsular stretching. Priapism is a complication seen in affected men.
 Aplastic crisis:
 Infection with human parvovirus B19 results in a severe but self-limiting
red cell aplasia  produces a very low hemoglobin  HF.
 Unlike in all other sickle crisis, the reticulocyte count is low.

37
  Investigation :
 Patients with SCA have a compensated anemia, usually around 60-80g/L.
 The blood film shows sickle cells, target cells and features of hyposplenism.
 A reticulocytotic is present. The presence of HbS can be demonstrated by
exposing red cells to a reducing agent such as sodium dithionate; HbA gives a
clear solution, whereas HbS polymerases to produce a turbid solution.
 Definitive diagnosis requires hemoglobin electrophoresis to demonstrate the
absence of HbA, 2-20% HbF and the predominance of HbS. Both parents of
affected individual will have sickle cell trait.

38