Functions of liver and different liver function tests

Major functions of Liver are the following

1. Blood glucose regulation
2. Synthesis of glycogen
3. Synthesis of triacyl glycerol
4. Synthesis of plasma proteins
5. Detoxification
6. Bile production, helps in digestion
7. Bilirubin metabolism

Biochemical test are done to assess the following
The hepatic function 

To detect hepatic injury

Patterns of abnormalities are more important than single test

May be normal in proven liver disease

Normal value never rules out liver Disease

Classification of liver function test based on laboratory findings

Hepatic excretory function is assessed with following tests

Serum Bilirubin

Urine: Bile Pigments, bile salt, urobilinogen

Liver enzymes

ALT,AST,ALP,GGT,5’ nucleotidase

Synthetic Function

Total Proteins

Serum albumin, globulins

Prothrombin time

Special Test

Ceruloplasmin

Ferritin

Alpha1 antitrypsin

Alpha fetoProteins

Classification of liver function  based on clinical aspects

Markers of liver dysfunction

Serum Bilirubin

Urine: Bile pigments, bile salt, urobilinogen

Total proteins, albumin

Prothrombin time

Blood ammonia

Markers of hepato cellular Injury

ALT,AST

Markers of cholestasis

ALP

GGT

5’ Nucleotidase 

Jones criteria for diagnosis of rheumatic fever

1. Acute rheumatic fever is a multi system disease.
2. Occur as a result of reaction to infection with group A streptococci.
3. Almost all the manifestations of rheumatic fever resolve completely except cardiac valvular damage.
4. This is mainly a disease of children aged 5 - 14 years. 
5. Females are more commonly affected.

Jones criteria for diagnosis of rheumatic fever

Major criteria

Carditis

Polyarthritis

Chorea

Erythema marginatum

Subcutaneous nodules

Minor criteria

Fever

Arthralgia

Previous rheumatic fever

Raised ESR

Leucocytosis

1st/2nd degree av block

Plus

Evidence for recent streptococcal infections infection

Recent scarlet fever

Raised antistreptolysin O

Positive throat culture

Major criterias 

1.Carditis

Valvular damage occur in carditis

Mitral valve is most commonly affected followed by aortic valve

Early valvular damage produce regurgitation

Later the leaf thickening, scarring and calcification result in valvular stenosis.

Patient will present with breathlessness,palpitation,chest pain,pleuritic central chest pain,pericardial rub, tachycardia, murmur,cardiac enlargement

Auscultation in carditis give the following findings

Soft systolic murmur in mitral area

Soft mid diastolic murmur(CARY COOMBS MURMUR) in mitral area

Pericardial friction rub due to pericarditis

Softening of the first heart sound(soft S1)

ECG will show evidence of ST or T wave changes. P-R interval prolongation.

2.Joint involvement

Knee, ankle, hip, and elbow are most commonly involved - asymmetric joint involvement is seen..

Acute painful inflammation of joint produce pain in rheumatic fever.

Typical joint involvent is migratory, moving from one joint to another over a period of hours.

Joint pain is severe and usually disabling.

If the joint involvement persists more than 1 or 2 days after starting salicylates it is unlikely to be due to acute rheumatic fever.

Most of the time sore throat is seen 2-4 weeks prior to the onset of joint symptoms.

Joint involvement is more prominent in adults and carditis in children.

3.Sydenhams chorea

Manifest late after initial infection with streptococcus(6 months or so).

Sidenham chorea manifest as spasmodic unintentional movements & possibly altered speech.

Spontaneous recovery is seen  within 6 weeks.

4. Erythema marginatum

They are red macules which fade in the centre, but remain red in the periphery.Never seen on the face.

5.Subcutaneous nodules

Painless, small (0.5-2 cm), mobile lumps seen beneath the skin overlying the bony prominences, particularly of the hands, feet, elbows and occiput.

It is a delayed manifestation of rheumatic fever

Usually seen 2-3 weeks after the onset of disease.

Significance of subcutaneous nodule is that if they are present associated carditis will be there.

Other clinical features 

Pleurisy

Pleural effusion

Pneumonia

High-grade fever (39°C) is the rule.

C-reactive protein (CRP) is elevated..

Elevated Erythrocyte sedimentation rate (ESR)

Investigations in Rheumatic fever

Evidence of systemic illness manifested as

Lleucocytosis,raised ESR, raised C reactive protein.

Evidence of preceeding streptococcal infection detected by the following tests

Throat swab culture: group A streptococcus.

Anti streptolysin o antibodies: > 200(adults), > 300(children

How will you identify Long QT Syndrome ?

Following notes will give you an idea how to calculate QT interval 

LQTS: Calculating the corrected  QTc

QTc= QT/square root of the RR interval

This will correct QT for the heart rate-  there is normally an inverse relation between heart rate and QTinterval,as one goes up/the other goes down and vice versa

Long QT  by definition  QTc in - males >470 ms 

                                                    - females of > 480 ms

Borderline prolonged QTc is present if the corrected QTc is 450-470 ms

Average QTc for someone with the LQTS is 490 ms

Diagnostic Criteria for LQTS

Certain points are given to each criteria

ECG findings

QTc

>480                                    3

460-470                               2

450 (male)                           1

Torsdade De Pointes            2

T-wave alternans                  1

Notched T wave in 3 leads   1

Low heart rate for age         0.5

Clinical History

Syncope with stress              2

              without stress          1

Congenital deafness             0.5

Family history

Definite LQTS                       1

Unexplained SCD in immediate family member that is less than 30 years of age     0.5

<1 points low probability of QT prolongation

2-3 points intermediate probability

 >4 points high probability

What is nonalcoholic fatty liver disease and what are its risk factors?

Definition of NAFLD 

This is a condition where patients having hepatic steatosis with or without inflammation and fibrosis, without any secondary causes of hepatic steatosis.

Following are the criteria for diagnosing nonalcoholic fatty liver disease

Imaging or biopsy should demonstrate  hepatic steatosis. 

Significant alcohol consumption  should be excluded.

Other causes of hepatic steatosis  should be  excluded.

What are the stages of NAFLD?

It include progression from steatosis, steatohepatitis to cirrhosis of liver

Steatosis ( Fatty liver )– NAFLD

Steatohepatitis – NASH

Cirrhosis

What are the disorders associated  with  NAFLD

Obesity

Systemic Hypertension

Hyperlipidemia

Insulin resistance or overt diabetes

PCOD

OSAS

Hypothyroidism

Hypopituitarism and hypogonadism

A family history of steatohepatitis or cryptogenic cirrhosis is  also implicated as a risk factor

Prevalence  of NAFLD

It is seen in 10-24% of general population.

2.6% of pediatric population have NAFLD.

It is the most common cause of cryptogenic cirrhosis

2/3rd of the obese patients have NASH.

90% of  morbidly obese patients have NASH.

Adrenal gland - Functional anatomy

Adrenal gland - They are suprarenal - they sit on top of the kidneys.

Each is composed of 2 distinct regions:

A. Adrenal Medulla

- the inner region

- comprises 20% of the gland

- secretes epinephrine and norepinephrine

- derived from ectoderm 

B. Adrenal Cortex

- the outer region

- comprises 80% of the gland

- secretes corticosteroids 

- derived from mesoderm

Following are the parts of adrenal cortex

1. Zona Glomerulosa (outermost region) - produces mineralocorticoids (aldosterone)  
2. Zona Fasiculata (middle region) - produces glucocorticoids (cortisol) as well as estrogens and androgens.
3. Zona Reticularis (innermost region)  produce  adrenal androgens.

Screening tests for acute and chronic polyarthritis

Screening tests in arthritis will help you to arrive at a diagnosis.

Screening tests for acute polyarthritis are the following

Blood cultures.

Antistreptolysin O titer.

Parvovirus B-19 immunoglobulin G and immunoglobulin M levels.

Hepatitis B serology.

ANA.

Others
HIV test, a rubella titer, an angiotensin-converting enzyme level . chest radiograph, and ANCA.

Screening tests for chronic polyarthritis are the following

Complete blood cell count.

ESR and CRP level.

ANAs.

Rheumatoid factor and CCP antibody.

Liver function tests, serum creatinine level.

Serum uric acid level.

Urinalysis.

OthersThyroid-stimulating hormone level, a serum ferritin level, and an iron saturation of serum transferrin.

Screening tests for diffuse arthralgias and myalgias

ESR and CRP - elevated in  inflammatory disease, including polymyalgia rheumatica.

Creatine kinase and aldolase level - myositis.

Thyroid test.

Chemistry profile (ie, calcium, phosphorus, electrolyte, glucose, total protein) - metabolic or endocrine disorders.

Others.

25-hydroxy vitamin D level -Osteomalacia.

Sacroiliac joint radiography - Ankylosing spondylitis, especially in woman <45 y with neck, chest wall, and low back pain).

HLA-B27 - In reactive arthritis.

Hepatitis B and C serology testing.

Serum and urine protein electrophoresis -to rule out multiple myeloma.

ANA and rheumatoid factor (if clinical features suggest RA, SLE, or another connective-tissue disease). 

Indications for dialysis therapy in acute kidney injury

Following are the indications for dialysis in acute kidney injury

1. Fluid overload that is refractory to diuretics.
2. Hyperkalemia  (serum potassium concentration > 6.5 meq/L) or rapidly rising potassium levels, refractory to medical therapy.
3. Metabolic acidosis (pH less than 7.1) in patients in whom the administration of bicarbonate is not indicated, such as those with volume overload (who would not tolerate the obligate sodium load), or those with lactic acidosis or ketoacidosis in whom bicarbonate administration has not been shown to be effective.
4. Signs of uremia, such as pericarditis, neuropathy, or an otherwise unexplained decline in mental status

How to measure Jugular venous pulse (JVP)

Objectives of examination of JVP 

Estimation of jugular venous pressure.

Assessment of wave forms.

Most important bedside test for assessment of volume status.

Assessment of waves give important clues regarding certain conditions.

Internal jugular vein  is preferred because 

It has no valves.

It is in direct line with S uperior vena cava  and right atrium.

Not passing through facial planes, unlikely to be compressed by other structures.

Usually best felt when patient’s trunk is inclined by less than 30.

If pressure is very high, better in sitting position.

If volume depleted, supine is better.

If increased pressure is suspected and pulsations not obtained, make the patient to sit up by the legs dangling over the side of bed. 

Surrogate marker of right sided pressure.

Distance between centre of right atrium and sternal ankle varies in many individuals.

At 40 degree, varies between 6-15cm.

Pulsation above clavicle at sitting position is usually abnormal.

Distance between right atrium  to clavicle is at least 10cm.

Estimation of an elevated pressure is important rather than the exact value.

1mm of Hg = 1.3cm of water.
How to measure jugular venous pressure-video

Formation and parts of spinal nerve

The Spinal cord receives information from trunk and limbs and controls the movement of the trunk and limbs. 

It has 31 paired Spinal nerves.

Formation of the spinal nerve 

Two linear series (6 - 8) of nerve fascicles are attached to the dorsolateral and ventrolateral aspects of the cord.The fascicles coalesce to form dorsal and ventral nerve roots.

The roots pass to their corresponding intervertebral foramina, near which they join to form the spinal nerve proper.

Dorsal root

Carry primary afferent neurons from the peripheral sensory receptors to the spinal cord and brain stem. 

Their cell bodies are in the dorsal root ganglia.

Ventral root

Carry : 

1.Efferent neurons (Lower motor neurons), their cell bodies are located in the spinal gray matter. 

2.Preganglionic autonomic neurons

Rami

Spinal Nerves are mixed.They contain both afferent and efferent fibers.

Each spinal nerve is divided into dorsal and ventral rami.

Dorsal ramus: It is thin. supplies muscles and skin of the back.

Ventral ramus:Is larger, supplies muscles and skin of the front of the body and limbs.Connected to the sympathetic chain by the white and grey rami.

Spinal segment and spine of vertebrae

The spinal cord is segmented. 

In the living, the approximate level of the segments is identified by the posterior spinous process of the vertebrae.

Cervical segments : One spine higher than their corresponding vertebrae. C7 segment is adjacent to C6 vertebra.

Thoracic segments : Two spines higher.

Lumbar segments : Three- four spines higher.

Exit of spinal nerves

1-7 spinal nerves : Exit above the upper seven cervical vertebrae.

C8 : Below 7th cervical vertebra.

T1 and the rest of the nerves: Below their corresponding vertebrae.

The Lumbar and Sacral nerves take an oblique course to reach the intervertebral foramina.

The resulting leash of nerve roots forms the Cauda Equina

Anatomy of Spinal cord

Beginning of spinal cord: 

Spinal cord begins at the foramen magnum as a continuation of the medulla Oblongata of the brain.

Shape of spinal cord: It is Cylindrical.

Length of spinal cord: Is about (45) cm.

It occupies upper 2/3 of the vertebral (spinal) canal of the vertebral column.

Levels of termination in different age groups

(1) Up till the 3rd month of fetal life: The spinal cord occupies the entire length of the vertebral canal.

(2) At birth : It terminates at the level of L3.

(3) Children : It ends at the Upper Border of the 3rd Lumbar vertebra.

(4) Adults : It terminates at the intervertebral disc (1st-2nd ) lumbar vertebrae.

Enlargement of spinal cord

Cervical : (C3- T1) Segments for the Brachial Plexus.

Lumbar : (L1- S3) Segments, for the Lumbar and Sacral Plexuses.

Mode of termination of spinal cord

Conus Medullaris : A conical termination caudal to the lumbar enlargement.

Filum terminale : A filament of connective tissue  arises from the tip of the conus. It is attached to the 1st Coccygeal vertebra.

Blood supply of internal capsule

Blood supply of internal capsule comes from 3 main arteries, they are
1) Lateral striate branches of middle cerebral artery.
2) Medial striate branches of anterior cerebral artery.
3) Anterior choroidal branches of internal carotid artery.

Lateral striate branches of middle cerebral artery supply
Anterior limb
Genu
Posterior limb
Basal ganglia

Medial striate branches of anterior cerebral artery supply
Anterior limb
Genu
Basal ganglia

Anterior choroidal branches of internal carotid supply
Posterior limb
Retrolenticular part

Anterior limb is supplied by the following arteries
Anterior cerebral artery through medial striate branch.
Middle cerebral artery through lateralstriate and lenticulostriate branches.

Genu is supplied by
Anterior cerebral artery through medial striate branch.
Middle cerebral artery through lateral striate and lenticulostriate branch.
Branches of internal carotid artery.

Posterior limb is supplied by
Middle cerebral artery through lateral striate and lenticulostriate branch. It is called Charcot’s artery of cerebral haemorrhage.
Anterior choroidal artery, a direct branch of internal carotid artery As it is long and slender it has tendency to get thrombosis.

Parts of Internal capsule

What is internal capsule?
Internal Capsule is a compact bundle of projection fibers (white matter) between caudate nucleus, thalamus medially and lentiform nucleus laterally.
It include 

Thalamocortical fibers

Corticothalamic fibers

Corticopontine fibers

Corticobulbar fibers

Corticospinal fibers

The fibers project from the cerebral cortex to the various nuclei of the extra pyramidal system (e.g.,the putamen and caudate nucleus).

This is a continuous sheet of fibres that forms the medial boundary of the lenticular nucleus.

Internal Capsule continues around posteriorly and inferiorly to partially envelop this nucleus.

Inferiorly, many of the fibers of the internal capsule funnel into the cerebral peduncles.
Superiorly, the fibers fan out into the corona radiata. Here, they travel in the cerebral white matter to reach their cortical origins or destinations.

The internal capsule is divided into 5 regions:

The anterior limb is the portion between the lenticular nucleus and the head of the caudate nucleus;

The posterior limb is the portion between the lenticular nucleus and the thalamus;

The genu is the portion at the junction of the above 2 parts and is adjacent to the interventricular foramen;

The retrolenticular part is the portion posterior to the lenticular nucleus;

The sublenticular part is the portion inferior to the lenticular nucleus.

Origin and spread of cardiac Impulse

Cardiac impulse originate in SAnode then reach the AV node there is AV nodal delay SAN - AVN -Delay Conduction in the ventricle Depolarization - Start - Left side of interventricular Septum Moves to the right Spreads down to the apex Returns along the ventricular wall to the AV groove Last part of Depolarization: Posterobasal portion of the Lt.Ventricle, Pulmonary Conus, Upper most portion of the Septum.

Different cardiac rhythms Sinus rhythm is normal Nodal rhythm Idio ventricular rhythm Normal pacemaker SAnode Abnormal pacemaker (ectopic pacemaker) A pacemaker elsewhere than the sinus node. They produce arrhythmia Common abnormal pacemaker: AV node or Purkinje fibers Atrial or ventricular muscle.

Definition of stroke

1.WHO definition

A neurological deficit.

Sudden onset.

With focal rather than global dysfunction.

In which, after adequate investigations, symptoms are presumed to be of non-traumatic vascular origin and last for > 24 hours

2. NINDS 2005 (National Institute of Neurological Disorders and Stroke)

When the blood supply to part of the brain is suddenly interrupted or when a blood vessel in the brain bursts.

3.TIA (Transient Ischemic Attack)

Neurological deficit of vascular origin lasts from few minutes to hours and resolves within 24 hours. 

 

Inclusion and exclusion criteria for thrombolysis in strok

Inclusion criteria

Clinical  signs and symptoms of definite acute stroke

Clear time of onset

Presentation within 3 hrs of acute onset

Haemorrhage excluded  by CT scan

Age 18 - 80 years old 

NIHSS less than 25

Consent to treat (every effort must be made to contact next of kin)

Exclusion criteria

Rapidly improving or minor stroke symptoms

Stroke or serious head injury 3 months

Major surgery, obstetrical delivery, external heart massage last 14 days, 

Seizure at onset of stroke

Prior stroke and concomitant diabetes

Severe haemorrhage last 21 days

Increase bleeding risk

History of central nervous damage (neoplasm, haemorrhage, aneurysm, spinal or intracranial surgery or haemorrhagic retinopathy)

Blood pressure above 185 mmHg systolic or 110 mmHg diastolic

Symptoms suggestive of SAH (even if CT is normal) 

Known clotting disorder

Patient on heparin or warfarin

Suspected iron deficient anaemia or thrombocytopenia

Suspected hypoglycaemia or hyper glycaemia >3 mmol/l > 22 mmol/l

Bacterial endocarditis, pericarditis

Acute pancreatitis

Ulcerative GI disease last 3 months, oesophageal varices, arterial-aneurysm, arterial/venous malformation.

Severe liver disease including cirrhosis, acute hepatitis  

Cerebrospinal Fluid (CSF)

The cerebrospinal fluid [CSF] is a clear, colorless transparent, tissue fluid that is present in the cerebral ventricles, spinal canal and subarachnoid spaces. It is an ultrafiltrate of blood plasma, normally CSF doesnot contain red blood cells and at most 4 white blood cells/µl may be present.

What are the  functions of CSF

CSF has both physical and metabolic function

It is   

A shock absorber

A mechanical buffer

Act as cushion between the brain and cranium

Act as a reservoir and regulates the contents of the cranium

Serves as a medium for nutritional exchange in CNS

Transport hormones and hormone releasing factors

Removes the metabolic waste products through absorption

The total CSF volume 

The total CSF volume in the adult is 150ml

Rate of formation of CSF 

20-25 ml/hour 

550 ml/day in adults.   Turns over 3.7 times a day

30-40 ml within the ventricles

About 110-120 ml in the subarachnoid space, of which 75-80 ml in spinal part and 25-30 ml in the cranial part.

Composition of CSF

Proteins = 20-40 mg/100 ml
Glucose = 50-65 mg/100 ml
Cholesterol = 0.2 mg/100 ml
Na+ = 147 meq/Kg  H2O
Ca+ = 2.3 meq/kg H2O
Urea = 12.0 mg/100 ml
Creatinine = 1.5 mg/100 ml
Lactic acid = 18.0 mg/100 ml

Characteristics of  CSF 

Colour = Clear, transparent fluid

Specific gravity = 1.004-1.007

Reaction = Alkaline 

Cells = 0-3/ cmm

Pressure = 60-150 mm of H2O 

The pressure of CSF is increased in standing, coughing, sneezing, crying, compression of internal Jugular vein which is called Queckenstedt’s sign.

The Circle of Willis

The Circle of Willis is a grouping of arteries at the base of the brain

It is named after an English physician named Thomas Willis, he discovered it and then published the findings in 1664

It is the joining area of several arteries at the inferior (bottom) side of the brain.The internal carotid arteries branch into smaller arteries at the Circle of Willis and supply oxygenated blood over 80% of the cerebrum

Formation of  Circle of Willis

The brain receives its blood supply from four main arteries:

2 internal carotid arteries 

2 vertebral arteries 

The vertebral arteries on each side  unite to form Basilar artery 

The basilar artery and the carotids together  form the circle of Willis below the hypothalamus

The circle of Willis is the origin of six large vessels that supply the cerebral cortex

The clinical presentation of vascular disease in the cerebral circulation is depended upon the  vessels or combinations of vessels that are involved.

Peculiarities of cerebral blood flow

The arteries and arterioles that supply blood to the brain are highly specialized,they include both vascular smooth muscle and endothelial cells and unlike vascular cells from the peripheral circulation or other vascular beds. 

The vascular smooth muscle is highly responsive to changes in pressure, a process called myogenic activity,which contributes to autoregulation of cerebral blood flow. 

The endothelial cells in the cerebral circulation are also highly specialized and they provide a barrier to fluid movement called the blood-brain barrier. 

ST Segment abnormalities in ECG

The ST segment represents period between ventricular depolarisation and repolarisation.
The ventricles are unable to receive any further stimulation.
The ST segment normally lies on the isoelectric line.

ST Segment Elevation

The ST segment lies above the isoelectric line.

Represents myocardial injury.

It is the hallmark of Myocardial Infarction.

The injured myocardium is slow to repolarise and remains more positively charged than the surrounding areas.

Other causes to be ruled out include pericarditis and ventricular aneurysm.

Myocardial Infarction

A medical emergency.

ST segment curves upwards in the leads looking at the threatened myocardium.

Presents within a few hours of the infarct.

Reciprocal ST depression may be present.

ST Segment Depression

Can be characterised as.

Downsloping.

Upsloping.

Horizontal.

Horizontal ST Segment Depression

Myocardial Ischaemia:

Stable angina - occurs on exertion, resolves with rest and/or GTN.

Unstable angina - can develop during rest.

Non ST elevation MI - usually quite deep, can be associated with deep T wave inversion.

Reciprocal horizontal depression can occur during AMI.

Downsloping ST segment depression can be caused by digoxin.

Upward sloping ST segment depression normal during exercise.

ECG abnormalities associated with ischaemia

Ischaemic Changes in ECG

S-T segment elevation

S-T segment depression

Hyper-acute T-waves

T-wave inversion

Pathological Q-waves

Left bundle branch block

Basic electrocardiography

Heart beat originates in the SA node.

Impulse spreads to all parts of the atria via internodal pathways .

ATRIAL contraction occurs.

Impulse reaches the AV node where it is delayed by 0.1second.

Impulse is conducted rapidly down the Bundle of His and Purkinje Fibres.

VENTRICULAR contraction occurs.

ECG Waveforms

Normal cardiac axis is downward and to the left.

ie the wave of depolarisation travels from the right atria towards the left ventricle.

When an electrical impulse travels towards a positive electrode, there will be a positive deflection on the ECG.

if the impulse travels away from the positive electrode, a negative deflection will be seen.

The P wave represents atrial depolarisation.

The PR interval is the time from onset of atrial activation to onset of ventricular activation.

The QRS complex represents ventricular depolarisation.

The S-T segment should be iso-electric, representing the ventricles before repolarisation.

The T-wave represents ventricular repolarisation.

The QT interval is the duration of ventricular activation and recovery.